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Long noncoding RNAs (lncRNAs) are known to regulate gene expression; however, in many cases, the mechanism of this regulation is unknown. One novel lncRNA relevant to inflammation and arachidonic acid (AA) metabolism is the p50-associated COX-2 extragenic RNA (PACER). We focused our research on the regulation of PACER in lung cancer. While the function of PACER is not entirely understood, PACER is known to play a role in inflammation-associated conditions. Our data suggest that PACER is critically involved in COX-2 transcription and dysregulation in lung cancer cells. Our analysis of The Cancer Genome Atlas (TCGA) expression data revealed that PACER expression is significantly higher in lung adenocarcinomas than normal lung tissues. Additionally, we discovered that elevated PACER expression strongly correlates with COX-2 expression in lung adenocarcinoma patients. Specific siRNA-mediated knockdown of PACER decreases COX-2 expression indicating a direct relationship. Additionally, we show that PACER expression is induced upon treatment with proinflammatory cytokines to mimic inflammation. Treatment with prostaglandin E2 (PGE2) induces both PACER and COX-2 expression, suggesting a PGE2-mediated feedback loop. Inhibition of COX-2 with celecoxib decreased PACER expression, confirming this self-regulatory process. Significant overlap between the COX-2 promotor and the PACER promotor led us to investigate their transcriptional regulatory mechanisms. Treatment with pharmacologic inhibitors of NF-κB or AP-1 showed a modest effect on both PACER and COX-2 expression but did not eliminate expression. These data suggest that the regulation of expression of both PACER and COX-2 is complex and intricately linked.

// Ketong Lai 1, 2, * , Siyuan Jia 1, * , Shanjuan Yu 1 , Jianming Luo 1, 2 and Yunyan He 1, 2 1 Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning 530021, China 2 Guangxi Key Laboratory of Thalassemia Research, Guangxi Zhuang Autonomous Region, Nanning 530021, China * These authors have contributed equally to this work Correspondence to: Yunyan He, email: yunyanhe@aliyun.com Jianming Luo, email: jmluo@aliyun.com Keywords: lncRNA, miRNA, ceRNA, β-thalassemia, hereditary persistence of fetal hemoglobin Received: January 26, 2017 Accepted: May 05, 2017 Published: May 29, 2017 ABSTRACT The implications of lncRNAs regarding fetal hemoglobin (HbF) induction in hemoglobin disorders remain poorly understood. In this study, microarray analysis was performed to profile lncRNAs, miRNAs and mRNAs in individuals with hereditary persistence of fetal hemoglobin (HPFH), β-thalassemia carriers with high HbF levels and healthy controls. The results show aberrant expression of 862 lncRNAs, 568 mRNAs and 63 miRNAs in the high-HbF group compared with the control group. Altered NR_001589, NR_120526, T315543, miR-486-3p, miR-19b-1-5p and miR-20a-3p expression was confirmed by quantitative reverse transcription-polymerase chain reaction, and Spearman correlation coefficients revealed significant positive correlations with HbF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed the hematopoietic cell lineage and apoptosis to be most significantly dysregulated in HbF induction. We analyzed coding genes near the lncRNAs and constructed a coding-noncoding co-expression network. Based on the results, lncRNAs likely contribute to increased HbF levels by activating expression of HBE1 and hematopoietic cell lineage-inducible molecules and by inhibiting that of apoptosis-inducible molecules. Finally, through construction of a competing endogenous RNA network, we found that 6 lncRNAs could bind competitively with miR-486-3p, resulting in increased HbF levels. Taken together, our findings provide new insights into the mechanisms of HbF induction and potentially provide new targets for the treatment of β-thalassemia major.

// Qiang Cai 1, * , Longyang Jin 1, * , Shouhua Wang 1 , Di Zhou 1 , Jiandong Wang 1 , Zhaohui Tang 1 and Zhiwei Quan 1 1 Department of General Surgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200092, China * These authors have contributed equally to this work Correspondence to: Zhiwei Quan, email: zhiwquan@sina.com Keywords: lncRNA UCA1, gallbladder cancer, EZH2, p21, E-cadherin Received: April 05, 2017 Accepted: April 28, 2017 Published: May 25, 2017 ABSTRACT A growing number of studies indicated that long non-coding RNAs (lncRNAs) determine some cellular processes in cancer, such as proliferation, metastasis and differentiation. Urothelial carcinoma associated 1 (UCA1), an lncRNA, had been reported for its overexpression and oncogenic effect on various human cancers. In this study, we found that UCA1 was significantly overexpressed in gallbladder cancer (GBC) and positively correlated with tumor size, lymph node metastasis, TNM stage and short survival time. Moreover, UCA1 promoted GBC cell proliferation and metastasis in vitro and tumor growth in vivo . Mechanically, we identified that UCA1 promoted GBC progression through recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p21 and E-cadherin, and epigenetically suppressing their transcript.

// Yonghao Zhan 1, 2, * , Yifan Li 1, * , Bao Guan 1, * , Xiaoying Chen 1, 2 , Zhicong Chen 1, 2 , Anbang He 1, 2 , Shiming He 1 , Yanqing Gong 1 , Ding Peng 1 , Yuchen Liu 1, 2 , Zhiming Cai 1, 2 , Xuesong Li 1 and Liqun Zhou 1 1 Department of Urology, Peking University First Hospital, The Institute of Urology, Peking University, National Urological Cancer Centre, Beijing, 100034, China 2 Department of Urology, State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China * These authors have contributed equally to this work Correspondence to: Liqun Zhou, email: zhoulqmail@sina.com Xuesong Li, email: pineneedle@sina.com Keywords: bladder cancer, biomarker, lncRNA CCEPR, PCNA, tumorigenesis Received: October 12, 2016 Accepted: April 22, 2017 Published: May 15, 2017 ABSTRACT Recent emerging evidences have showed that long non-coding RNAs play important regulatory roles in diverse biological processes of tumor development and progression. CCEPR (cervical carcinoma expressed PCNA regulatory lncRNA) is a novel identified lncRNA that acts as a potential biomarker and involves in development and progression of cervical carcinoma. Nevertheless, we know nothing about the clinical significance and molecular mechanism of CCEPR in bladder cancer. In this study, we found that CCEPR was significantly up-regulated in bladder cancer. Furthermore, up-regulated CCEPR expression was positively correlated with advanced TNM stage and higher histological grade. Moreover, further experiments demonstrated that CCEPR promotes cell proliferation and suppresses cell apoptosis in bladder cancer. Mechanistically, we found CCEPR upregulates the expression of PCNA in mRNA and protein level to promote cancer growth. In conclusions, these findings demonstrated that CCEPR plays an important regulatory role in bladder cancer and may serve as a potential diagnostic biomarker and therapeutic target.

// Jia Liu 1, * , Jieru Lin 2, * , Yingqi Li 4 , Yunyuan Zhang 3 and Xian Chen 3 1 Department of Pharmacy, Guiyang Maternal and Child Health Care Hospital, Guiyang 550003, China 2 Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang 550002, China 3 Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao 266003, China 4 Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China * These authors contributed equally to this work Correspondence to: Xian Chen, email: cxkakicoco2014@163.com Keywords: cancer, prognosis, long non-coding RNA, taurine upregulated gene 1 Received: February 25, 2017 Accepted: April 29, 2017 Published: May 13, 2017 ABSTRACT LncRNA TUG1 has been demonstrated to be aberrantly expressed in several types of cancer and maybe serve as a prognostic marker for cancer patients. However, most individual studies have been limited by small sample sizes and controversial results. Therefore, this meta analysis was conducted to analyze available data to delineate the potential clinical application of lncRNA TUG1 on cancer prognosis, lymph node metastasis and tumor progression. Up to February 20, 2017, literature collections were conducted by comprehensive searching electronic databases, including Cochrane Library, PubMed, Embase, BioMed Central, Springer, ScienceDirect, ISI Web of Knowledge, together with three Chinese databases. The hazard ratios (HR) with 95% confidence interval (95% CI) were calculated to assess the strength of the association. Eight studies with a total of 840 cancer patients were included in the present meta analysis. The results indicated that elevated lncRNA TUG1 significantly predicted unfavorable overall survival (OS) (HR = 2.06, 95% CI: 1.23–3.45, P = 0.006), but failed to show incline to lymph node metastasis (HR: 1.16, 95% CI: 0.82–1.62, P = 0.40) and disease progression (III/IV vs. I/II: HR 1.16, 95% CI: 0.74–1.81, P = 0.52). In stratified analyses, a significantly unfavorable OS associated with elevated lncRNA TUG1 was observed in both bladder cancer (HR = 2.98, 95% CI: 1.84–4.83, P < 0.0001) and other system cancer (HR = 2.63, 95% CI: 1.42–4.87, P = 0.002), but not respiratory system cancer (HR = 0.93, 95% CI: 0.30–2.82, P = 0.895). The results indicated that increased lncRNA TUG1 was an independent prognostic biomarker for unfavorable OS but may not susceptible to lymph node metastasis and tumor progression in cancer patients.

// Mingjing Shao 1, * , Guangdong Chen 2, * , Fengli Lv 3 , Yanyan Liu 4 , Hongjun Tian 5 , Ran Tao 6, 8 , Ronghuan Jiang 7, 9 , Wei Zhang 2 and Chuanjun Zhuo 2, 4, 5 1 National Integrated Traditional and Western Medicine Center for Cardivascular Disease, China-Japan Friendship Hospital, Beijing, China 2 Department of Psychological Medicine, Wenzhou Seventh People’s Hospital, Wenzhou, China 3 Department of Rehabilitation, The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China 4 Department of Psychological Medicine, Tianjin Anning Hospital, Tianjin, China 5 Department of Psychological Medicine, Tianjin Anding Hospital, Tianjin, China 6 Department of Psychological Medicine, Beijing Shijian Integrated Medicine Science Institute, Beijing, China 7 Department of Psychological Medicine, Chinese People’s Liberation Army General Hospital, Beijing, China 8 Department of Psychological Medicine, Chinese Land Force General Hospital, Beijing, China 9 Department of Psychological Medicine, Chinese People’s Liberation Army, Medical School, Beijing, China * These authors contributed equally to this work Correspondence to: Chuanjun Zhuo, email: chuanjunzhuotjmh@163.com Keywords: TINCR, CaMKII, EZH2, cardiac hypertrophy Received: March 20, 2017 Accepted: April 26, 2017 Published: May 10, 2017 ABSTRACT In the previous study, we established a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC) and found that the expression of long non-coding RNAs TINCR was downregulated in myocardial tissue. The present study was designed to determine the potential role of TINCR in the pathogenesis of cardiac hypertrophy. Our results showed that enforced expression of TINCR could attenuate cardiac hypertrophy in TAC mice. Angiotensin II (Ang-II) was found to be associated with reduced TINCR expression and increased hypertrophy in cultured neonatal cardiomyocytes. RNA-binding protein immunoprecipitation assay confirmed that TINCR could directly bind with EZH2 in cardiomyocytes. The results of chromatin immunoprecipitation assay revealed that EZH2 could directly bind to CaMKII promoter region and mediate H3K27me3 modification. Knockdown of TINCR was found to reduce EZH2 occupancy and H3K27me3 binding in the promoter of CaMKII in cardiomyocytes. In addition, enforced expression of TINCR was found to decrease CaMKII expression and attenuate Ang-II-induced cardiomyocyte hypertrophy. Furthermore, our results also showed that Ang-II could increase CaMKII expression in cardiomyocytes, which consequently contributed to cellular hypertrophy. In conclusion, our findings demonstrated that TINCR could attenuate myocardial hypertrophy by epigenetically silencing of CaMKII, which may provide a novel therapeutic strategy for cardiac hypertrophy.

// Yu Fang 1 , Jingxuan Wang 1 , Feng Wu 2 , Ying Song 1 , Shu Zhao 1 and Qingyuan Zhang 1 1 Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Nangang District, Harbin 151000, Heilongjiang Province, China 2 Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin 151000, Heilongjiang Province, China Correspondence to: Qingyuan Zhang, email: qyzhangdoctor@sina.com Keywords: LncRNA-HOXA-AS2, miR-520c-3p, breast cancer, growth, metastasis Received: January 16, 2017 Accepted: March 01, 2017 Published: May 02, 2017 ABSTRACT The long non-coding RNA (lncRNA) HOXA cluster antisense RNA2 (HOXA-AS2) has recently been shown to be dysregulated and involved in the progression of several cancers. However, the biological role and clinical significance of HOXA-AS2 in the carcinogenesis of breast cancer are still unclear. In the present study, we found that HOXA-AS2 was up-regulated in human breast cancer tissues and cell lines and associated with clinicopathological characteristics. Silencing of HOXA-AS2 inhibited the progression of breast cancer cells in vitro and in vivo . Furthermore, microarray profiling indicated that HOXA-AS2 serves as an endogenous sponge by directly binding to miR-520c-3p and down-regulating miR-520c-3p expression. We demonstrated that HOXA-AS2 controls the expression of miR-520c-3p target genes, TGFBR2 and RELA, in breast cancer cells. Therefore, our study may provide a better understanding of the pathogenesis of breast cancer and suggests that HOXA-AS2 may be a potential prognostic and therapeutic target in breast cancer.

// Lin Yu 1 , Lina Tai 1 , Lifang Zhang 1 , Yi Chu 1 , Yixing Li 1 and Lei Zhou 1 1 State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, P.R. China Correspondence to: Yixing Li, email: liyixing39@163.com Lei Zhou, email: zhoulei@gxu.edu.cn Keywords: lncRNA, pig, obesity, QTL Received: April 28, 2017 Accepted: May 15, 2017 Published: May 26, 2017 ABSTRACT Objectives: Current studies have revealed that long non-coding RNA plays a crucial role in fat metabolism. However, the difference of lncRNA between lean (Duroc) and obese (Luchuan) pig remain undefined. Here, we investigated the expressional profile of lncRNA in these two pigs and discussed the relationship between lncRNA and fat deposition. Materials and Methods: The Chinese Luchuan pig has a dramatic differences in backfat thickness as compared with Duroc pig. In this study, 4868 lncRNA transcripts (including 3235 novel transcripts) were identified. We determined that patterns of differently expressed lncRNAs and mRNAs are strongly tissue-specific. The differentially expressed lncRNAs in adipose tissue have 794 potential target genes, which are involved in adipocytokine signaling pathways, the PI3k-Akt signaling pathway, and calcium signaling pathways. In addition, differentially expressed lncRNAs were located to 13 adipose-related quantitative trait loci which include 65 QTL_ID. Subsequently, lncRNA and mRNA in the same QTL_ID were analyzed and their co-expression in two QTL_ID were confirmed by qPCR. Conclusions: Our study provides an insight into mechanism behind the fat metabolic differences between the two breeds and lays an important groundwork for further research regarding the regulatory role of lncRNA in obesity development.

// Tian An 1, * , Teng Zhang 2, * , Fei Teng 1 , Jia-Cheng Zuo 1 , Yan-Yun Pan 1 , Yu-Fei Liu 3 , Jia-Nan Miao 1 , Yu-Jie Gu 1 , Na Yu 1 , Dan-Dan Zhao 1 , Fang-Fang Mo 1 , Si-Hua Gao 1 and Guangjian Jiang 1 1 Diabetes Research Center, Beijing University of Chinese Medicine, Beijing, China 2 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China 3 The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China * These authors have contributed equally to this work Correspondence to: Si-Hua Gao, email: sihuagaopaper@sina.com Guangjian Jiang, email: guangjianjiang@sina.com Keywords: long non-coding RNA, paternal inheritance, genetic vector, obesity Received: April 03, 2017 Accepted: April 24, 2017 Published: May 24, 2017 ABSTRACT Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.

Papillary thyroid carcinoma (PTC) is the most frequent type of malignant thyroid tumor. Several lncRNA signatures have been established for prognosis prediction in some cancers. However, the prognostic value of lncRNAs has not been investigated in PTC yet. In this study, we performed genome-wide analysis of lncRNA expression profiles in a large cohort of PTC patients from The Cancer Genome Atlas and identified 111 differentially expressed lncRNAs between tumor and non-tumor samples and between recurrent and recurrence-free samples. From the 111 differentially expressed lncRNAs, four independent lncRNA biomarkers associated with prognosis were identified and were integrated into a four-lncRNA signature which classified the patients of training dataset into the high-risk group and low-risk group with significantly different overall survival (p=0.016, log-rank test). The prognostic value of the four-lncRNA signature was validated in the independent testing dataset. Multivariate analysis indicated that the four-lncRNA signature was an independent prognostic predictor. Moreover, identified four lncRNA biomarkers demonstrates good performance in predicting disease recurrence with AUC of 0.833 using leave one out cross-validation. Our study not only highlighted the potential role for lncRNAs to improve clinical prognosis prediction in patients with PTC and but also provided alternative biomarkers and therapeutic targets for PTC patients.

// Jianbin Gu 1 , Yong Li 1 , Liqiao Fan 1 , Qun Zhao 1 , Bibo Tan 1 , Kelei Hua 1 and Guobin Wu 1 1 Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Hebei, China Correspondence to: Yong Li, email: li_yong_hbth@126.com Keywords: stomach adenocarcinoma, expression profile, long non-coding RNA, co-expression, tumorigenesis Received: September 08, 2016 Accepted: April 11, 2017 Published: April 21, 2017 ABSTRACT Aim: Stomach adenocarcinoma (STAD) is a common malignancy worldwide. This study aimed to identify the aberrantly expressed long non-coding RNAs (lncRNAs) in STAD. Results: Total of 74 DElncRNAs and 449 DEmRNAs were identified in STAD compared with paired non-tumor tissues. The DElncRNA/DEmRNA co-expression network was constructed, which covered 519 nodes and 2993 edges. The qRT-PCR validation results of DElncRNAs were consistent with our bioinformatics analysis based on RNA-sequencing. The DEmRNAs co-expressed with DElncRNAs were significantly enriched in gastric acid secretion, complement and coagulation cascades, pancreatic secretion, cytokine-cytokine receptor interaction and Jak-STAT signaling pathway. The expression levels of the nine candidate DElncRNAs in TCGA database were compatible with our RNA-sequencing. FEZF1-AS1, HOTAIR and LINC01234 had the potential diagnosis value for STAD. Materials and Methods: The lncRNA and mRNA expression profile of 3 STAD tissues and 3 matched adjacent non-tumor tissues was obtained through high-throughput RNA-sequencing. Differentially expressed lncRNAs/mRNAs (DElncRNAs/DEmRNAs) were identified in STAD. DElncRNA/DEmRNA co-expression network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predict the biological functions of DElncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was subjected to validate the expression levels of DEmRNAs and DElncRNAs. Moreover, the expression of DElncRNAs was validated through The Cancer Genome Atlas (TCGA) database. The diagnosis value of candidate DElncRNAs was accessed by receiver operating characteristic (ROC) analysis. Conclusions: Our work might provide useful information for exploring the tumorigenesis mechanism of STAD and pave the road for identification of diagnostic biomarkers in STAD.

// Jieyu Zhou 1, 2, * , Shengda Cao 1, * , Wenming Li 1 , Dongmin Wei 1 , Zhentao Wang 2 , Guojun Li 3, 4 , Xinliang Pan 1 and Dapeng Lei 1 1 Department of Otorhinolaryngology, Qilu Hospital, Shandong University, Key Laboratory of Otolaryngology, NHFPC - Shandong University, Jinan, Shandong, 250012, P.R. China 2 Department of Otorhinolaryngology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200011, P.R. China 3 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 4 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA * These authors contributed equally to this work Correspondence to: Xinliang Pan, email: panxinl915@126.com Dapeng Lei, email: leidapeng@sdu.edu.cn Keywords: hypopharyngeal squamous cell carcinoma, radioresistance, lncRNA, mRNA, microarray Received: December 05, 2016 Accepted: April 10, 2017 Published: April 21, 2017 ABSTRACT Radioresistance remains a major problem in the treatment of patients with hypopharyngeal squamous cell carcinoma (HSCC). Long noncoding RNAs (lncRNAs) have important roles in the development, invasion, and metastasis of various tumors, including HSCC, but little is known about the role of lncRNAs in cancer radioresistance. The aim of this study was to identify radioresistance-related lncRNAs and mRNAs in radioresistant (RS) hypopharyngeal cancer subclone RS-FaDu cells. In this study, we performed microarray analysis to find the differences in time-course lncRNA and mRNA expression profiles between RS-FaDu and parent FaDu cells after 4 Gy radiation therapy, whose reliability was confirmed by validation experiment. Among these consistently dysregulated lncRNAs, we found that some lncRNAs (e.g., TCONS_00018436) might control resistance of HSCC cells to radiation. Furthermore, our bioinformatics analyses from mRNA/lncRNA microarray data showed that certain lncRNAs or mRNAs potentially are involved in radioresistance of HSCC. Our results from this study laid the foundation for further investigating the roles of these lncRNAs and mRNAs as promising candidates in the occurrence and development of HSCC radioresistance.

// Jiyoung Kim 1 , Ji Heon Noh 1 , Seung-Kyu Lee 1 , Rachel Munk 1 , Alexei Sharov 1 , Elin Lehrmann 1 , Yongqing Zhang 1 , Weidong Wang 1 , Kotb Abdelmohsen 1 and Myriam Gorospe 1 1 Laboratory of Genetics and Genomics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA Correspondence to: Jiyoung Kim, email: kim.jiyoung@elixirgen.com Myriam Gorospe, email: myriam-gorospe@nih.gov Keywords: lncRNA, proliferation, mitosis Received: January 22, 2017 Accepted: March 22, 2017 Published: April 19, 2017 ABSTRACT Some long noncoding RNAs (lncRNAs) can regulate gene expression programs, in turn affecting specific cellular processes. We sought to identify the mechanism through which the lncRNA OIP5-AS1 , which is abundant in the cytoplasm, suppressed cell proliferation. Silencing of OIP5-AS1 in human cervical carcinoma HeLa cells triggered the appearance of many aberrant (monopolar, multipolar, misaligned) mitotic spindles. Through a combination of approaches to pull down mRNAs bound to OIP5-AS1 and identify proteins differentially expressed when OIP5-AS1 was silenced, we identified a subset of human cell cycle regulatory proteins encoded by mRNAs that interacted with OIP5-AS1 in HeLa cells. Further analysis revealed that GAK mRNA, which encodes a cyclin G-associated kinase important for mitotic progression, associated prominently with OIP5-AS1 . The interaction between these two transcripts led to a reduction in GAK mRNA stability and GAK protein abundance, as determined in cells in which OIP5-AS1 levels were increased or decreased. Importantly, the aberrant mitotic cell division seen after silencing OIP5-AS1 was partly rescued if GAK was simultaneously silenced. These findings indicate that the abnormal mitoses seen after silencing OIP5-AS1 were caused by an untimely rise in GAK levels and suggest that OIP5-AS1 suppresses cell proliferation at least in part by reducing GAK levels.

// Ming Li 1 , Ying Wang 2, 3 , Liang Cheng 4 , Wanting Niu 5 , Guoan Zhao 6 , Jithin K. Raju 7 , Jun Huo 1 , Bin Wu 1 , Bo Yin 1 , Yongsheng Song 1 and Renge Bu 1 1 Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China 2 Department of Nuclear Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China 3 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA 4 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA 5 Department of Orthopedics, Brigham and Women’s Hospital, VA Boston Healthcare System, Harvard Medical School, Boston, Massachusetts 02115, USA 6 School of Network Education, Beijing University of Posts and Telecommunications, Hebei, Beijing 100088, P.R. China 7 Department of Clinical Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China Correspondence to: Renge Bu, email: burg@sj-hospital.org Keywords: renal cell carcinoma, lncRNA, diagnosis, prognosis, therapy Received: November 18, 2016 Accepted: March 20, 2017 Published: April 12, 2017 ABSTRACT Renal cell carcinoma is one of the most common malignancy in adults, its prognosis is poor in an advanced stage and early detection is difficult due to the lack of molecular biomarkers. The identification of novel biomarkers for RCC is an urgent and meaningful project. Long non-coding RNA (lncRNA) is transcribed from genomic regions with a minimum length of 200 bases and limited protein-coding potential. Recently, lncRNAs have been greatly studied in a variety of cancer types. They participate in a wide variety of biological processes including cancer biology. In this review, we provide a new insight of the profiling of lncRNAs in RCC and their roles in renal carcinogenesis, with an emphasize on their potential in diagnosis, prognosis and potential roles in RCC therapy.

// Youmao Tao 1 , Tao Han 1 , Tao Zhang 1 , Chong Ma 1 , Caixia Sun 1 1 Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China Correspondence to: Caixia Sun, email: scx_cjuh@163.com Keywords: LncRNA CHRF, miR-489, TWIST1/EMT, metastasis, CRC Received: March 10, 2017 Accepted: March 28, 2017 Published: April 05, 2017 ABSTRACT microRNA-489 (miR-489) is a novel cancer-related miRNAs and functions as a tumor suppressor in human cancers. While, the clinical significance of miR-489 and its role in colorectal cancer (CRC) remain rarely known. Here, we found that the levels of miR-489 in CRC tissues were significantly lower than those in matched tumor-adjacent tissues. Furthermore, decreased levels of miR-489 also observed in CRC cell lines compared to HIEC cells. Clinicopathological analysis revealed that miR-489 underexpression was positively correlated with advanced pT stage, pN stage and AJCC stage. Moreover, miR-489 low expressing CRC patients showed a obvious shorter survival. Functionally, miR-489 restoration inhibited cell migration and invasion as well as epithelial-mesenchymal transition (EMT) in HCT116 cells, while miR-489 loss facilitated these cellular processes in SW480 cells. In vivo experiments revealed that miR-489 overexpression reduced the number of metastatic nodules in nude mice liver. Notably, TWIST1 was recognized as a direct downstream target of miR-489 in CRC cells. Interestingly, TWIST1 restoration abrogated the effects of miR-489 on CRC cells with enhanced cell migration, invasion and EMT process. Furthermore, overexpression of long noncoding RNA cardiac hypertrophy-related factor (lncRNA CHRF) was inversely correlated with miR-489 expression in CRC tissues. CHRF knockdown increased the expression of miR-489 and suppressed EMT events of HCT116 cells, while CHRF overexpression showed opposite effects on miR-489 expression and EMT in SW480 cells. Taken together, this work support the first evidence that lncRNA CHRF-induced miR-489 loss facilitates metastasis and EMT process of CRC cells probably via TWIST1/EMT signaling pathway.

// Jian Fang 1 , Fuhao Qiao 1 , Jingjing Tu 1 , Jinfeng Xu 1 , Fangfang Ding 1 , Yun Liu 1 , Bufugdi Andreas Akuo 1 , Jianpeng Hu 2 and Shihe Shao 1 1 Department of Pathogenic Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China 2 Department of Urinary Surgery, Zhenjiang First People’s Hospital, Zhenjiang, Jiangsu 212013, China Correspondence to: Shihe Shao, email: 351564372@qq.com Keywords: NEAT1, cancer, OS, meta-analysis, poor prognosis Received: September 07, 2016 Accepted: April 11, 2017 Published: April 26, 2017 ABSTRACT The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA. Many studies have reported that NEAT1 plays critical oncogenic roles and facilitates tumorigenesis of various human cancers. High NEAT1 expression is associated with a poor prognosis in cancer patients. This meta-analysis was conducted to assess the association between NEAT1 levels and survival times of cancer patients. Overall survival (OS) was the primary endpoint. Thirteen publications with 1,496 cancer patients from 5 databases (PubMed, EMBASE, Cochrane Library, Wiley Online Library, and Medline) met the criteria for this meta-analysis. Results of the analysis showed that NEAT1 expression in human cancer was significantly associated with OS (hazard ratio [HR]=1.53, 95% confidence interval [CI]: 1.39–1.68), including digestive system tumor (HR=1.54, 95% CI: 1.37–1.73) and respiratory carcinomas (HR=1.44, 95% CI: 1.11–1.85). The results also indicated that NEAT1 expression was highly associated with tumor size (>3 cm vs. ≤3 cm; odds ratio [OR]=2.51, 95% CI: 1.27–4.99; p =0.009), TNM stage (III+IV vs. I+II; OR=4.17, 95% CI: 2.42–7.18; p =0.00001), and distant metastasis (OR=2.73, 95% CI: 1.28–5.79; p =0.01). However, there was no significant association with differentiation (poor vs. well + moderate, OR=1.45, 95% CI: 0.72–2.91) and lymph node metastasis (OR=1.39, 95% CI: 0.54–3.60). This meta-analysis showed that NEAT1 expression may be a useful biomarker for predicting a poor prognosis in patients with cancer.

// Peng Zhang 1, * , Peihua Cao 1, * , Xiaofeng Zhu 2 , Mingxin Pan 1 , Kebo Zhong 1 , Rui He 2 , Yang Li 1, 3 , Xingyuan Jiao 2 , Yi Gao 1, 3, 4 1 Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong, P. R. China 2 Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P. R. China 3 Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong, P. R. China 4 State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, Guangdong, P. R. China * These authors contributed equally to this work Correspondence to: Yi Gao, email: gaoyi6146@163.com Xingyuan Jiao, email: jiaoxingyuan@hotmail.com Keywords: HOXA-AS2, LncRNA, GBC, metastasis, EMT Received: January 19, 2017 Accepted: March 09, 2017 Published: March 25, 2017 ABSTRACT Gallbladder carcinoma (GBC) is the most common malignancy of the bile duct and patients with GBC have extremely poor prognoses. Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and cancer progression. However, the function of lncRNAs in the progression of GBC remains largely unknown. Here, we reported that HOXA cluster antisense RNA2 (HOXA-AS2) was upregulated in GBC. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited GBC cells proliferation by causing G1 arrest and promoting apoptosis, whereas HOXA-AS2 overexpression promoted cell growth. Further functional assays indicated that HOXA-AS2 overexpression significantly promoted GBC cell migration and invasion by promoting EMT. Taken together, our study demonstrates that HOXA-AS2 could act as a functional oncogene in GBC, as well as a potential therapeutic target to inhibit GBC metastasis.

// Yanyan Tang 1, 2, 3 , Yi He 2, 4 , Lei Shi 5 , Liting Yang 2 , Jinpeng Wang 2 , Yu Lian 2 , Chunmei Fan 2 , Ping Zhang 6 , Can Guo 2 , Shanshan Zhang 1 , Zhaojian Gong 2, 5 , Xiayu Li 3 , Fang Xiong 1 , Xiaoling Li 1, 2, 3 , Yong Li 2, 7 , Guiyuan Li 1, 2, 3 , Wei Xiong 1, 2, 3 and Zhaoyang Zeng 1, 2, 3 1 The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China 2 The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China 3 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China 4 Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China 5 Department of pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China 6 School of Information Science and Engineering, Central South University, Changsha, Hunan, China 7 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA Correspondence to: Zhaoyang Zeng, email: zengzhaoyang@csu.edu.cn Lei Shi, email: shilei1000@hotmail.com Keywords: long non-coding RNA, AFAP1-AS1 , programmed death 1 ( PD-1 ), prognosis, nasopharyngeal carcinoma (NPC) Received: January 13, 2017 Accepted: February 15, 2017 Published: March 24, 2017 ABSTRACT Nasopharyngeal carcinoma (NPC) carries a high potential for metastasis and immune escape, with a great risk of relapse after primary treatment. Through analysis of whole genome expression profiling data in NPC samples, we found that the expression of a long non-coding RNA (lncRNA), actin filament-associated protein 1 antisense RNA 1 ( AFAP1-AS1 ), is significantly correlated with the immune escape marker programmed death 1 ( PD-1 ). We therefore assessed the expression of AFAP1-AS1 and PD-1 in a cohort of 96 paraffin-embedded NPC samples and confirmed that AFAP1-AS1 and PD-1 are co-expressed in infiltrating lymphocytes in NPC tissue. Moreover, patients with high expression of AFAP1-AS1 or PD-1 in infiltrating lymphocytes were more prone to distant metastasis, and NPC patients with positive expression of both AFAP1-AS1 and PD-1 had the poorest prognosis. This study suggests that AFAP1-AS1 and PD-1 may be potential therapeutic targets in NPC and that patients with co-expression of AFAP1-AS1 and PD-1 may be ideal candidates for future clinical trials of anti-PD-1 immune therapy.

// Yongbin Zheng 1 , Chao Yang 1 , Shilun Tong 1 , Yu Ding 1 , Wenhong Deng 1 , Dan Song 1 , Kuang Xiao 1 1 Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China Correspondence to: Yongbin Zheng, email: zhengyongbinhb@163.com Keywords: colorectal cancer, variation, genetic, TINCR, lncRNA Received: January 05, 2017 Accepted: February 13, 2017 Published: March 24, 2017 ABSTRACT Colorectal cancer (CRC) accounts for the leading causes of cancer-related morbidity and mortality. However, a large part of heritable factors are warranted to be explored. Long non-coding RNAs (lncRNAs) serve critical roles in cancer development and progression. Herein, we explored effect of genetic variants of Tissue differentiation-inducing non-protein coding RNA (TINCR), a key lncRNA required for somatic tissue differentiation and tumor progression, on risk and progression of CRC. Three tagSNPs, including rs2288947, rs8105637, and rs12610531, were evaluated in in a two-stage, case-control study. Two SNPs, rs2288947 and rs8105637, were significantly associated with susceptibility of CRC in both stages. When pooled together, the allele G was significantly associated with 23% decreased risk of CRC (OR=0.77; 95% CI=0.67-0.88; P value = 1.2×10 -4 )for SNP rs2288947. While for SNP rs8105637, the allele A was significantly associated with 22% increased risk of CRC (OR=1.22; 95% CI=1.09-1.37; P value = 6.2×10 -4 ). The two SNPs were also statistically associated with occurrence of lymph node metastasis of CRC. The carriers of allele G are less likely to get lymph node metastasis (OR=0.77; 95% CI=0.63-0.94; P value = 0.011) for rs2288947, and the carriers of allele A are more likely to get lymph node metastasis (OR=1.22; 95% CI=1.03-1.43; P value = 0.019) for rs8105637. These results suggest that lncRNA TINCR polymorphisms may be implicated in the development and progression of CRC.

// Fang-Teng Liu 1, 2, * , Qing Dong 2, 3, * , Hui Gao 4, * and Zheng-Ming Zhu 1 1 Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, P.R. China 2 Medical School of Nanchang University, Nanchang 330000, Jiangxi Province, P.R. China 3 The Third Radiotherapy Department, Tumor Hospital of Jiangxi Province, Nanchang 330029, Jiangxi Province, P.R. China 4 The Children’s Hospital of Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, P.R. China * These authors have contributed equally to this work Correspondence to: Zheng-Ming Zhu, email: zzm8654@163.com Keywords: UCA1, lncRNA, carcinoma, digestive system, prognosis Received: November 10, 2016 Accepted: February 28, 2017 Published: March 23, 2017 ABSTRACT Background: Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. Results: The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52–2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45–2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30–3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. Materials and methods: A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. Conclusions : Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers.

Urine UCA1 has been reported as a potential novel diagnostic biomarker for bladder cancer in several studies, but their results are inconsistent. As a result of this, a diagnostic meta-analysis to assess the diagnostic performance of urine UCA1 in detecting bladder cancer was conducted. A systematic electronic and manual search was performed for relevant literatures through PubMed, Cochrane library, Chinese Wan Fang and the China National Knowledge Infrastructure (CNKI) databases up to December 30, 2016. The quality of the studies included in this meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. All analyses were conducted using stata12.0 software. Six studies collectively included 578 bladder cancer patients and 562 controls met the eligible criteria. The overall diagnostic accuracy was measured by the following: sensitivity 0.81 (95% CI = 0.75-0.86), specificity 0.86 (95% CI = 0.73-0.93), positive likelihood ratio 5.85 (95% CI = 2.72-12.57), negative likelihood 0.22 (95% CI = 0.15-0.32), diagnostic odds ratio 27.01 (95% CI = 8.69-83.97), and area under the curve 0.88 (95% CI = 0.85-0.91). Meta-regression analysis suggested that ethnicity significantly accounted for the heterogeneity of sensitivity. Deeks' funnel plot asymmetry test (P = 0.33) suggested no potential publication bias. According to our results, urine UCA1 has greater diagnostic value in diagnosing bladder cancer, however further research studies with more well-designed and large sample sizes are required to confirm our findings.

// He Li 1,2 , Si-Qing Ma 1,2 , Jin Huang 1,2 , Xiao-Ping Chen 1,2,3 and Hong-Hao Zhou 1,2,3 1 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P.R. China 2 Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P.R. China 3 Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, P. R. China Correspondence to: Xiao-Ping Chen, email: // Hong-Hao Zhou, email: // Keywords : colorectal cancer, metastasis, lncRNAs, review Received : November 17, 2016 Accepted : February 20, 2017 Published : March 17, 2017 Abstract Colorectal cancer (CRC) is the 3 rd most common malignancies worldwide. Metastasis is responsible for more than 90% CRC patients’ death. Long noncoding RNAs (lncRNAs) are an important class of transcribed RNA molecules greater than 200 nucleotides in length. With the development of whole genome sequencing technologies, they have been gained more attention. Accumulating evidences suggest that abnormal expression of lncRNAs in diverse diseases are involved in various biological functions such as proliferation, apoptosis, metastasis and differentiation by acting as epigenetic, splicing, transcriptional or post-transcriptional regulators. Aberrant expression of lncRNAs has also been found in CRC. Besides, recent studies have indicated that lncRNAs play important roles in tumourigenesis and cancer metastasis. They participate in the process of metastasis by activing or inhibiting the metastatic pathways. However, their functions on the development of cancer metastasis are poorly understood. In this review, we highlight the findings of roles for lncRNAs in CRC metastasis and review the metastatic pathways of lncRNAs leading to cancer metastasis in CRC, including escape of apoptosis, epithelial-mesenchymal transition (EMT), angiogenesis and invasion, migration and proliferation. Furthermore, we also discuss the potential clinical application of lncRNAs in CRC as diagnostic markers and therapeutic targets.

// Yawei Wang 1 , Ye Hu 2 , Gang Wu 3 , Ye Yang 1 , Yanqing Tang 4 , Wanchuan Zhang 3 , Kaiyu Wang 3 , Yu Liu 1 , Xin Wang 1 , Tiemin Li 1 1 Department of Geriatric Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China 2 Department of Nephrology, Liaoning Provincial People’s Hospital, Shenyang, Liaoning 110000, China 3 Department of General Surgery, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning 110001, China 4 Department of Psychology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China Correspondence to: Gang Wu, email: 18660232387@163.com Keywords: PCAT-14, miR-372, HCC, proliferation, invasion Received: November 30, 2016 Accepted: March 08, 2017 Published: March 16, 2017 ABSTRACT Long non-coding RNAs (lncRNAs) regulate oncogenesis by inducing methylation of CpG islands to silence target genes. Here we show that the lncRNA PCAT-14 is overexpressed in patients with hepatocellular carcinoma (HCC), and is associated with a poor prognosis after surgery. Our results demonstrate that PCAT-14 promotes proliferation, invasion, and cell cycle arrest in HCC cells. In addition, PCAT-14 inhibits miR-372 expression by inducing methylation of the miR-372 promoter. Simultaneously, miR-372 eliminates the effects of PCAT-14 on proliferation, invasion, and cell cycle in HCC cells. Moreover, PCAT-14 regulates expression of ATAD2 and activation of the Hedgehog pathway via miR-372. These findings indicate that PCAT-14 plays an important role in HCC, and may serve as a novel prognostic factor and therapeutic target.

Competing endogenous RNA (ceRNA) is a newly proposed mechanism that describes a crosstalk among lncRNAs, mRNAs and their shared miRNAs. In this study, the role of miR-338-3p (miR-338) in the progression of esophageal cancer and its involve in the ceRNA regulatory circuit lncRNA-Snhg1/CST3 were explored. MiR-338 displayed a 30% decreased expression in esophageal squamous cell carcinoma tissues compared with the adjacent. Then, proto-oncogene CST3 was predicted and validated as a target gene of miR-338. Gain-and-loss-function experiments indicated that miR-338 suppressed expression of CST3 protein (also Cystatin C, CysC), promoted expression of apoptotic proteins caspase-8/3, attenuated esophageal carcinoma cell growth and induced its apoptosis. In addition, lncRNA-Snhg1 was significantly upregulated in esophageal carcinoma tissues and promoted esophageal carcinoma cell growth. Furthermore, our results from bioinformatics, luciferase reporter gene and RNA pull-down assays indicated that Snhg1 could be directly bound by miR-338. Snhg1 acted as a non-degradable sponge to relieve the suppression on CST3 caused by miR-338. In conclusion, lncRNA-Snhg1 promoted cell proliferation by acting as a non-degradable sponge for the tumor suppressor miR-338 in esophageal cancer cells.

// Shuangtao Zhao 1, * , Shuangsang Fang 2, * , Yanhua Liu 3, 4, 5, * , Xixi Li 3, 6 , Shengyou Liao 2 , Jinwen Chen 2 , Jingjia Liu 2 , Lianhe Zhao 2 , Hui Li 2 , Wei Zhou 3, 4, 5 , Wenzhi Shen 3, 4, 5 , Xiaoli Dong 3, 4, 5 , Rong Xiang 3, 4, 5 , Luhua Wang 1 , Yi Zhao 2 1 Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China 2 The Key Laboratory of Intelligent Information Processing, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China 3 The School of Medicine, Nankai University, Tianjin, China 4 The Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin, China 5 The Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Tianjin, China 6 Department of Pathology, Nankai University, Tianjin, China * Co-first author Correspondence to: Rong Xiang, email: rxiang@nankai.edu.cn Luhua Wang, email: wlhwq@yahoo.com Yi Zhao, email: biozy@ict.ac.cn Keywords: diffuse large B-cell lymphoma, long non-coding RNA, NONHSAG026900, prognosis, biomarker Received: January 17, 2017 Accepted: February 24, 2017 Published: March 13, 2017 ABSTRACT Long non-coding RNAs are known to be involved in cancer progression, but their biological functions and prognostic values are still largely unexplored in diffuse large B-cell lymphoma. In this study, long non-coding RNAs expression was characterized in 1,403 samples including normal and diffuse large B-cell lymphoma by repurposing 7 microarray datasets. Compared with any stage of normal B cells, NONHSAG026900 expression was significantly decreased in tumor samples. And in germinal center B-cell subtype, the significantly higher expression of NONHSAG026900 indicated it was a favorable prognosis biomarker. Then the prognostic power of NONHSAG026900 was validated with another independent dataset and NONHSAG026900 improved the predictive power of International Prognostic Index as an independent factor. Moreover, functional prediction and validation demonstrated that NONHSAG026900 could inhibit cell cycle activity to restrain tumor proliferation. These findings identified NONHSAG026900 as a novel prognostic biomarker and offered a new therapeutic target for diffuse large B-cell lymphoma patients.

// Chenhui Ma 1, 2, 3, * , Guannan Wu 1, 2, * , Qingqing Zhu 1, 2 , Hongbing Liu 1, 2 , Yanwen Yao 1, 2 , Dongmei Yuan 1, 2 , Yafang Liu 1, 2, 4 , Tangfeng Lv 1, 2 , Yong Song 1, 2 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China 2 Nanjing University Institute of Respiratory Medicine, Nanjing 210002, China 3 Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China 4 Nanfang Hospital, Southern Medical University, Guangzhou 510515, China * These authors contributed equally to this work Correspondence to: Tangfeng Lv, email: bairoushui@163.com Yong Song, email: yong_song6310@yahoo.com Keywords: long noncoding RNA, linc00673, NSCLC, metastasis, HOXA5 Received: January 02, 2017 Accepted: February 15, 2017 Published: March 13, 2017 ABSTRACT Metastasis of cancer cells is a key impediment to favorable outcomes of cancer treatment. Functional roles of long noncoding RNAs in several biological processes, including metastasis, have recently been discovered. In our previous work, we reported a positive correlation of increased expression of linc00673 in NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased proliferation of NSCLC cells, both, in vitro and in vivo . In this study, we demonstrate that ectopic expression of linc00673 promotes migration and invasion of NSCLC cells. Furthermore, our results indicate that linc00673 could silence HOXA5 expression by recruiting epigenetic repressor, EZH2, at its promoter regions. HOXA5 was identified as a tumor suppressor gene, which inhibited NSCLC cell metastasis by regulating cytoskeletal remodeling. To summarize, we for the first time identified the role of lin00673 in promoting invasion and migration of NSCLC cells. Insights from this study may help to identify novel therapeutic targets for NSCLC.

// Xiaoxiong Wang 1, 2, * , Fei Peng 1, 2, * , Liang Cheng 3, * , Guang Yang 1, 2 , Daming Zhang 1, 2 , Jiaqi Liu 1, 2 , Xin Chen 1, 2 , Shiguang Zhao 1, 2 1 Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang Province, 150001, People’s Republic of China 2 Institute of Brain Science, Harbin Medical University, Nangang District, Harbin, Heilongjiang Province, 150001, People’s Republic of China 3 College of Bioinformatics Science and Technology, Harbin Medical University, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China * These authors contributed equally to this work Correspondence to: Shiguang Zhao, email: guangsz@hotmail.com Keywords: long noncoding RNA (lncRNA), urothelial cancer associated 1 (UCA1), cancer, prognosis Received: August 10, 2016 Accepted: February 27, 2017 Published: March 09, 2017 ABSTRACT Urothelial cancer associated 1 (UCA1) as an oncogenic long non-coding RNA (LncRNA) was aberrantly upregulated in various solid tumors. Numerous studies have demonstrated overexpression of UCA1 is an unfavorable prognostic indicator in cancer patients. This study aimed to further explore the prognosis role and clinical significance of UCA1 in cancer. Eligible studies were recruited by a systematic search in PubMed, Embase, Cochrane Library and Web of Science databases. A total of 19/16 studies with 1587/1291 cancer patients were included to evaluate the association between UCA1 expression and overall survival (OS) and clinicopathological factors of malignancies by computing hazard ratio (HR), odds ratios (OR) and confidence interval (CI). The meta-analysis indicated overexpression of UCA1 was significantly correlated with unexpected OS in patients with cancer (pooled HR = 1.85, 95% CI 1.62–2.10, p < 0.001). There was also a significantly negative association between high level of UCA1 and poor grade cancer (pooled OR = 2.74, 95% CI 2.04–3.70, p < 0.001) and positive lymphatic metastasis (pooled OR = 2.43, 95% CI 1.72–3.41, p < 0.001). In conclusion, our study suggested that UCA1 was correlated with more advanced clinicopathological features and poor prognosis as a novel predictive biomarker of patients with various tumors.

// Yue Sun 1, * , Shi-Dai Jin 2, * , Quan Zhu 3, * , Liang Han 4, 6, * , Jing Feng 1, 5 , Xi-Yi Lu 2 , Wei Wang 3 , Feng Wang 3 , Ren-Hua Guo 2 1 Department of Oncology, Yancheng Third People’s Hospital, The Affiliated Yanchen Hospital of Southeast University Medicine College, Yancheng, Jiangsu, China 2 Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 3 Department of Thoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 4 Department of Oncology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, College of Medicine, Southeast University, Xuzhou, Jiangsu, China 5 Department of Oncology, Jiangsu Shengze Hospital, Suzhou, Jiangsu, China 6 Department of Oncology, Yancheng Third People’s Hospital, The Affiliated Yanchen Hospital of Southeast University Medicine College, Yancheng, Jiangsu, China * These authors contributed equally to this work and should be regarded as joint first authors Correspondence to: Ren-Hua Guo, email: rhguo@njmu.edu.cn Keywords: LncRNAs, LUCAT1, p21, p57, non-small cell lung cancer (NSCLC) Received: June 09, 2016 Accepted: February 27, 2017 Published: March 09, 2017 ABSTRACT Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor–node–metastasis (TNM) stage and overall survival (OS). Further experiments showed that LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo . Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest. We further demonstrated that LUCAT1 was associated with polycomb repressor complexes (PRC2) and that this association was required for epigenetically repression of p21 and p57, thus contributing to the regulation of NSCLC cell cycle and proliferation. In summary, our results show that LUCAT1 could regulate tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.

// Shlomit Brodie 1 , Hae Kyung Lee 2 , Wei Jiang 2 , Simona Cazacu 2 , Cunli Xiang 2 , Laila M. Poisson 3 , Indrani Datta 3 , Steve Kalkanis 2 , Doron Ginsberg 1, * and Chaya Brodie 1, 2, * 1 Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel 2 Davidson Laboratory of Cell Signaling and Tumorigenesis, Hermelin Brain Tumor Center, Department of Neurosurgery, Detroit, MI, USA 3 Department of Public Health Sciences, Center for Bioinformatics, Henry Ford Hospital, Detroit, MI, USA * These authors have contributed equally to this work Correspondence to: Chaya Brodie, email: chaya@brodienet.com Keywords: TALNEC2, long non-cording RNAs, glioblastoma, glioma stem cells, mesenchymal transformation Received: October 07, 2016 Accepted: February 06, 2017 Published: March 07, 2017 ABSTRACT Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need to identify molecular mechanisms that play a role in patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM with poor prognosis, in GBM specimens derived from short-term survivors and in glioma cells and glioma stem cells (GSCs). Silencing of TALNEC2 inhibited cell proliferation and arrested the cells in the G1\S phase of the cell cycle in various cancer cell lines. In addition, silencing of TALNEC2 decreased the self-renewal and mesenchymal transformation of GSCs, increased sensitivity of these cells to radiation and prolonged survival of mice bearing GSC-derived xenografts. Using miRNA array analysis, we identified specific miRNAs that were altered in the silenced cells that were associated with cell-cycle progression, proliferation and mesenchymal transformation. Two of the downregulated miRNAs, miR-21 and miR-191, mediated some of TALNEC2 effects on the stemness and mesenchymal transformation of GSCs. In conclusion, we identified a novel E2F1-regulated lncRNA that is highly expressed in GBM and in tumors from patients of short-term survival. The expression of TALNEC2 is associated with the increased tumorigenic potential of GSCs and their resistance to radiation. We conclude that TALNEC2 is an attractive therapeutic target for the treatment of GBM.

// Yu-Mei Chen 1, * , Hua Li 2, * , Yi Fan 2 , Qi-Jun Zhang 2 , Xing Li 2 , Li-Jie Wu 2 , Zi-jie Chen 2 , Chun Zhu 3 , Ling-Mei Qian 2 1 Department of Emergency, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China 2 Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P. R. China 3 Department of Pediatrics, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210004, P. R. China * These authors contributed equally to this work Correspondence to: Ling-Mei Qian, email: lmqian@njmu.edu.cn Chun Zhu, email: zhifangxibao@163.com Keywords: neonatal mouse, heart, regeneration, lncRNAs Received: August 15, 2016 Accepted: February 20, 2017 Published: March 03, 2017 ABSTRACT Previous studies have shown that mammalian cardiac tissue has a regenerative capacity. Remarkably, neonatal mice can regenerate their cardiac tissue for up to 6 days after birth, but this capacity is lost by day 7. In this study, we aimed to explore the expression pattern of long noncoding RNA (lncRNA) during this period and examine the mechanisms underlying this process. We found that 685 lncRNAs and 1833 mRNAs were differentially expressed at P1 and P7 by the next-generation high-throughput RNA sequencing. The coding genes associated with differentially expressed lncRNAs were mainly involved in metabolic processes and cell proliferation, and also were potentially associated with several key regeneration signalling pathways, including PI3K-Akt, MAPK, Hippo and Wnt. In addition, we identified some correlated targets of highly-dysregulated lncRNAs such as Igfbp3, Trnp1, Itgb6, and Pim3 by the coding-noncoding gene co-expression network. These data may offer a reference resource for further investigation about the mechanisms by which lncRNAs regulate cardiac regeneration.

// Yanliang Yang 1 , Shunli Wang 1 and Teng Li 1 1 Bone Tumour & Bone Disease Department I, Zhengzhou Orthopaedics Hospital, Zhengzhou Orthopedics Hospital Affiliated to Henan University, Henan, China Correspondence to: Yanliang Yang, email: // Keywords : osteosarcoma, lncRNA, prognosis, meta-analysis Received : November 01, 2016 Accepted : March 10, 2017 Published : March 22, 2017 Abstract Long non-coding RNAs (lncRNAs) are emerging as promising prognostic biomarkers in an expanding list of malignant neoplasms. Here, we sought to investigate the strength of associations between lncRNA signatures and clinical outcomes in osteosarcoma. We conducted a systematic search of the online databases from inception to July 2016. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for the primary endpoints of overall survival (OS), progression-free survival (PFS) or event-free survival (EFS) were extracted and meta-analyzed. Our results manifested that altered lncRNAs expression was markedly associated with worse OS (univariate analysis: HR = 3.20, 95% CI: 2.42-4.24, P = 0.000; multivariate analysis: HR = 2.66, 95% CI: 1.92-3.69, P = 0.000), PFS (HR = 2.05, 95% CI: 1.32-3.18, P = 0.001) and EFS (HR = 4.37, 95% CI: 1.64-11.66, P = 0.003) times among osteosarcoma patients. In the pooled analyses stratified by clinicopathological features, levels of lncRNAs were closely correlated with tumor size (pooled P = 0.001), tumor stage (pooled P = 0.003), and distant metastasis (pooled P = 0.002) in osteosarcoma. The results obtained in our work suggest that altered lncRNA signatures predict unfavorable clinical outcomes and are acceptable to be potential prognostic biomarkers in forecasting prognosis of osteosarcoma.

// Miaojuan Wang 1 , Xuejun Dong 1 , Yi Feng 1 , Honggang Sun 1 , Ningping Shan 1 and Tao Lu 1 1 Clinical Laboratory Center of Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China Correspondence to: Tao Lu, email: taolushaox@126.com Keywords: lncRNA, SPRY4-IT1, prognosis, overall survival, meta-analysis Received: February 14, 2017 Accepted: March 06, 2017 Published: March 31, 2017 ABSTRACT Recent studies have emphasized the important role of long non-coding RNAs (lncRNAs) in cancer development. The present study performed a meta-analysis to investigate whether lncRNA, SPRY4 Intronic Transcript 1(SPRY4-IT1 ) can be served as a potential biomarker for prognosis in human cancers. The eligible studies were collected by searching multiple online databases (Pubmed, EMBASE, CNKI, Web of Science and Google Scholar) and meta-analysis was performed to explore the association between the expression levels of SPRY4-IT1 and overall survival (OS), disease-free survival (DFS) and clinicopathological parameters. A total of 1329 patients from 13 studies were included for meta-analysis. The meta-analysis results showed that high expression level of SPRY4-IT1 was significantly associated with shorter OS in cancer patients (HR = 3.20, 95% CI: 2.59-3.90, P

Contains fulltext : 174142.pdf (Publisher’s version ) (Open Access) For many years, research on the biology underlying bladder cancer focused on protein-coding genes which cover only about 3% of the human genome. Recently, it was discovered that a large part of the human genome is actively transcribed as long non-coding RNAs (lncRNAs). LncRNAs are master regulators of gene expression and several lncRNAs were shown to play a role in bladder cancer development and progression. Here, we analyzed lncRNA expression in muscle-invasive bladder cancer (MIBC) using the MiTranscriptome database of cancer lncRNA expression profiles, and we studied their function in bladder cancer-derived tumor cells. Analysis of the MiTranscriptome lncRNA expression data revealed four MIBC subgroups, which partially overlapped with the four mRNA clusters identified by The Cancer Genome Atlas consortium. Up-regulation of three lncRNAs CAT266, CAT1297, and CAT1647 in bladder cancer, in comparison to normal urothelium, was confirmed in an independent series of normal, non-muscle invasive (NMIBC) and MIBC tissue samples. Furthermore, expression levels of CAT1297 were found to be correlated with disease-free and overall survival in MIBC. Knockdown of CAT266, CAT1297, and CAT1647 decreased cell viability and colony formation, due to the induction of apoptosis. In conclusion, our data show that lncRNAs expression is de-regulated in MIBC and three aberrantly expressed transcripts regulate proliferation and apoptosis. Our data indicate that lncRNAs play an important role in MIBC development and progression and are a treasure chest for the discovery of new biomarkers.

Metastatic melanoma of the skin has a high mortality despite the recent introduction of targeted therapy and immunotherapy. Long non-coding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides in length that lack protein-coding potential. There is growing evidence that lncRNAs play an important role in gene regulation, including oncogenesis. We present 13 lncRNA genes involved in the pathogenesis of cutaneous melanoma through a variety of pathways and molecular interactions. Some of these lncRNAs are possible biomarkers or therapeutic targets for malignant melanoma.

// Yan Pan 1, * , Jing Chen 1, * , Leilei Tao 1, * , Kai Zhang 1, * , Rui Wang 1 , Xiaoyuan Chu 1 , Longbang Chen 1 1 Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China * The authors contributed equally to this work Correspondence to: Longbang Chen, email: chenlongbang@yeah.net Keywords: lung adenocarcinoma (LAD), linc-ROR, miR-145, FSCN1, chemoresistance Received: January 16, 2017 Accepted: March 16, 2017 Published: March 25, 2017 ABSTRACT Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) contributes to the development and progression of lung adenocarcinoma (LAD), however the underlying mechanism of action of lncRNAs remains unclear. It is well known that the effective treatment of cancers has been hindered by drug resistance in the clinical setting. Epithelial-mesenchymal transition (EMT) has been recognized to be involved in acquiring drug resistance, cell migration and invasion properties in several types of cancer. Docetaxel-resistant LAD cells established previously in our lab present chemoresistant and mesenchymal features. Long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR), was first discovered in induced pluripotent stem cells (iPSCs) and was upregulated in docetaxel-resistant LAD cells. In this study, we tried to make clarification of lincRNA-related mechanisms underlying EMT followed by acquired resistance to chemotherapy in LAD. In order to hit the mark, we made use of multiple methods including microarray analysis, qRT-PCR, western blotting analysis, loss/gain-of-function analysis, luciferase assays, drug sensitivity assays, wound-healing assay and invasion assay. We found that decreased expression of linc-ROR effectively reversed EMT in docetaxel-resistant LAD cells and sensitized them to chemotherapy. The function of linc-ROR exerted in LAD cells depended on the sponging of miR-145, therefore, releasing the miR-145 target FSCN1, and thus contributing to the acquisition of chemoresistance and EMT phenotypes of docetaxel-resistant LAD cells. Our findings revealed that linc-ROR might act as potential therapeutic target to overcome chemotherapy resistance in LAD.

// Yanqing Huo 1 , Qingbo Li 1 , Xiqian Wang 1 , Xiejia Jiao 1 , Jiachun Zheng 1 , Zhiqiang Li 1 and Xiaohan Pan 2 1 Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China 2 Department of Health Management, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China Correspondence to: Xiaohan Pan, email: xiaohanpan@163.com Keywords: MALAT1, osteosarcoma, TGF-β, metastasis, EZH2 Received: January 25, 2017 Accepted: March 06, 2017 Published: March 24, 2017 ABSTRACT Osteosarcoma is the most common type of bone cancer, especially in children and young adults. Recently, long noncoding RNAs (lncRNAs) have emerged as new prognostic markers and gene regulators in several cancers, including osteosarcoma. In this study, we investigated the contributions of the lncRNA MALAT1 in osteosarcoma with a specific focus on its transcriptional regulation and its interaction with EZH2. Our results showed that MALAT1 was significantly increased in osteosarcoma specimens and cell lines. ROC curve analysis showed that MALAT1 had a higher area under the curve than alkaline phosphatase, and Kaplan-Meier survival analysis indicated that patients with high serum levels of MALAT1 showed reduced survival rate. Knockdown of MALAT1 decreased osteosarcoma cell invasion and promoted E-cadherin expression. Mechanistic investigations showed that MALAT1 was transcriptionally activated by TGF-β. Additionally, EZH2 is highly expressed and associated with the 3’ end region of lncRNA MALAT1 in osteosarcoma, and this association finally suppressed the expression of E-cadherin. Subsequently, our gain and loss function assay showed that MALAT1 overexpression promoted cell metastasis and decreased E-cadherin level, however, this effect was partially reversed by EZH2 knockdown. In conclusion, our work illuminates that lncRNA MALAT1 is a potential diagnostic and prognostic factor in osteosarcoma and further demonstrates how MALAT1 confers an oncogenic function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.

// Longci Sun 1 , Chunhui Jiang 1 , Chunjie Xu 1 , Hanbing Xue 2 , Hong Zhou 1 , Lei Gu 1 , Ye Liu 1 , Qing Xu 1 1 Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China 2 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China Correspondence to: Qing Xu, email: celebrationxu@yeah.net Keywords: colorectal cancer, long noncoding RNA, RP11-708H21.4, RNA sequencing, tumorigenesis Received: November 02, 2016 Accepted: February 20, 2017 Published: March 02, 2017 ABSTRACT Long non-coding RNAs (lncRNAs) serve critical roles in cancer development and progression. Herein, through next generation RNA sequencing and experimental validations, we determined the expression status of RP11-708H21.4 in colorectal cancer (CRC) and explored its clinical significance and biological functions in CRC. Differentially expressed lncRNAs from CRC samples and corresponding normal mucosa tissues was screened through RNA sequencing, and RP11-708H21.4 was selected for further experimental validation. The expression levels of RP11-708H21.4 in CRC tissues and cell lines were determined using qRT-PCR. Also, the relationship between the clinicopathological features and RP11-708H21.4 expression was analyzed. Cell viability was examined by CCK-8 and colony assays; cell migration and invasion were detected by transwell assays; cell cycle and cell apoptosis were analyzed by flow cytometry. The chemosensitivity of CRC cells to 5-Fluorouracil (5-FU) was also determined using CCK-8 assay. CRC xenograft tumor models were established to determine the biological functions of RP11-708H21.4 in vivo . Levels of cell cycle-related proteins and AKT/mTOR pathway-related proteins were detected by western blot assay. RP11-708H21.4 expression was aberrantly decreased in CRC, and its expression was closely associated with aggressive clinicopathologic features and unfavorable prognosis of CRC patients. Overexpressed RP11-708H21.4 suppresses CRC cell proliferation through inducing G1 arrest. Moreover, up-regulation of RP11-708H21.4 inhibits cell migration and invasion, causes cell apoptosis, and enhances 5-FU sensitivity of CRC cells. Finally, increased RP11-708H21.4 expression blocked AKT/mTOR pathway, and repressed in vivo CRC xenograft tumor growth. The results indicated that RP11-708H21.4 might have potential roles as a biomarker and a therapeutic target for CRC.

// Nan Wang 1, * , Qing Qiao 1, * , Guoqiang Bao 1 , Tao Wu 1 , Yizhou Li 2 , Jingjie Li 3 , Jianguo Lu 1 , Xianli He 1 1 Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, China 2 Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010050, China 3 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi’an, Shaanxi, 710069, China * These authors have contributed equally to this work Correspondence to: Jianguo Lu, email: lujianguoLJG123@163.com Xianli He, email: wanghe@fmmu.edu.cn Keywords: gastric cancer, colorectal cancer, single-nucleotide polymorphism, susceptibility, case-control Received: September 26, 2016 Accepted: January 10, 2017 Published: February 26, 2017 ABSTRACT Here, we genotyped eleven single-nucleotide polymorphisms (SNPs) and evaluated their association with the risk of developing gastric cancer (GC) or colorectal cancer (CRC) in 1,790 Han Chinese participants (588 GC patients, 499 CRC patients, and 703 healthy controls). Statistically analysis showed that the “C” allele of rs2689154 in MIPEPP2 was associated with a decreased risk of GC (odds ratio [OR] = 0.81, 95 % confidence interval [CI]: 0.66-0.99, P = 0.041), whereas the “T” allele of rs12615966 in LOC284998 was associated with a 1.29-fold increase in the risk of GC (OR = 1.29, 95% CI: 1.03-1.63, P = 0.029). Additionally, genetic model analyses showed that rs2689154 was associated with a reduced risk of GC under the recessive model (adjusted OR = 0.46, 95% CI: 0.22-0.98, P = 0.037), and rs12615966 in FOXF1 was associated with an increased risk of GC in both the dominant and log-additive models after adjusted for age and gender (adjusted OR = 1.36, 95% CI: 1.02-1.81, P = 0.033; adjusted OR = 1.36, 95% CI: 1.05-1.75, P = 0.018, respectively). We also observed that rs2178146 in FOXF1 was associated with an increased risk of CRC in the recessive model (adjusted OR = 1.90, 95% CI: 1.05-3.45, P = 0.034). Our results confirmed that rs2689154 in MIPEPP2 was significantly decreased GC risk, but rs12615966 in LOC284998 was significantly increased GC risk, and rs2178146 in FOXF1 was associated with increased CRC risk in the Han Chinese population.

// Xue Gong 1,2 , Zurab Siprashvili 3 , Okyaz Eminaga 1,4 , Zhewei Shen 2 , Yusuke Sato 5,6 , Haruki Kume 6 , Yukio Homma 6 , Seishi Ogawa 5 , Paul A. Khavari 3 , Jonathan R. Pollack 2 and James D. Brooks 1 1 Department of Urology, School of Medicine, Stanford University, Stanford, California, USA 2 Department of Pathology, School of Medicine, Stanford University, Stanford, California, USA 3 Program in Epithelial Biology, School of Medicine, Stanford University, Stanford, California, USA 4 Department of Urology, University Hospital Cologne, Cologne, Germany 5 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 6 Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Correspondence to: Jonathan R. Pollack, email: // James D. Brooks, email: // Keywords : lincRNA, renal cell carcinoma, kidney cancer, biomarker, prognostication Received : November 04, 2016 Accepted : January 24, 2017 Published : February 24, 2017 Abstract Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior, and prognostic biomarkers are needed to stratify patients for appropriate management. We sought to determine whether long intergenic non-coding RNAs (lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data on 466 ccRCC cases (randomized into discovery and validation sets) annotated for ~21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival-predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and validated in an independent University of Tokyo cohort ( P =0.004). In multivariable analysis, SLINKY expression predicted overall survival independent of tumor stage and grade [TCGA HR=3.5 (CI, 2.2-5.7), P < 0.001; Tokyo HR=8.4 (CI, 1.8-40.2), P = 0.007], and by decision tree, ROC and decision curve analysis, added independent prognostic value. In ccRCC cell lines, SLINKY knockdown reduced cancer cell proliferation (with cell-cycle G 1 arrest) and induced transcriptome changes enriched for cell proliferation and survival processes. Notably, the genes affected by SLINKY knockdown in cell lines were themselves prognostic and correlated with SLINKY expression in the ccRCC patient samples. From a screen for binding partners, we identified direct binding of SLINKY to Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK), whose knockdown recapitulated SLINKY knockdown phenotypes. Thus, SLINKY is a robust prognostic biomarker in ccRCC, where it functions possibly together with HNRNPK in cancer cell proliferation.

// Lifen Liu 1 , Xin Chen 1 , Ying Zhang 1 , Yanrong Hu 1 , Xiaoqing Shen 1 and Weipei Zhu 1 1 Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China Correspondence to: Weipei Zhu, email: zwp333xx_suzhou@126.com Keywords: lincRNA, endometrial cancer Received: October 20, 2016 Accepted: January 24, 2017 Published: February 22, 2017 ABSTRACT It is generally known that the human genome makes a large amount of noncoding RNAs compared with coding genes. Long non-coding RNAs (lncRNAs) which composed of more than 200 nucleotides have been described as the largest subclass of the non-coding transcriptome in human noncoding RNAs. Existing research shows that lncRNAs exerted biological functions in various tumors via participating in both oncogenic and tumor suppressing pathways. The previous studies indicated that lncRNA taurine upregulated 1 (TUG1) play important roles in the initiation and progression of malignancies. In this study,based on previous research, we investigated the expression and biological role of the lncRNA-TUG1. We analyzed the relationship between lncRNA-TUG1and endometrial carcinoma (EC) in a total 104 EC carcinoma specimens, compared with that in normal tissues. We found that lncRNA-TUG1 expression in cancer tissues was significantly higher than that in adjacent tissues. Through a series of experiments, the results demonstrated that lncRNA-TUG1 enhances the evolution and progression of EC through inhibiting miR-299 and miR-34a-5p.

// Yanlin Zhang 1, * , Mengyao Zhang 2, * , Weiting Xu 3 , Jianchang Chen 3 , Xiang Zhou 3 1 Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China 2 Department of Cardiology, The First People’s Hospital of Kunshan Affiliated to Jiangsu University, Kunshan, China 3 Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China * These authors have contributed equally to this work Correspondence to: Xiang Zhou, email: zhou-xiang@suda.edu.cn Keywords: H19, miR-675, PA2G4, apoptosis, dilated cardiomyopathy Received: January 02, 2017 Accepted: February 08, 2017 Published: February 20, 2017 ABSTRACT In the previous study, we generated a rat model of dilated cardiomyopathy (DCM) induced by adriamycin and found that the expression of lncRNA H19 was significantly upregulated in myocardial tissue. The present study was aimed to investigate the potential role of H19 in the pathogenesis of adriamycin-induced DCM. H19 knockdown in the myocardium of DCM rats attenuated cardiomyocyte apoptosis and improved left ventricular structure and function. Adriamycin treatment was associated with elevated H19 and miR-675 expression and increased apoptosis in neonatal cardiomyocytes. Enforced expression of miR-675 was found to induce apoptosis in cardiomyocytes with adriamycin treatment and H19-siRNA transfection. The 3’-untranslated region of PA2G4 was cloned downstream of a luciferase reporter construct and cotransfected into HEK293 cells with miR-675 mimic. The results of luciferase assay showed that PA2G4 was a direct target of miR-675. The expression of PA2G4 was reduced in cardiomyocytes transfected with miR-675 mimic. Moreover, H19 knockdown was found to increase PA2G4 expression and suppress apoptosis in cardiomyocytes exposed to adriamycin. In conclusion, our study suggests that H19/miR-675 axis is involved in the promotion of cardiomyocyte apoptosis by targeting PA2G4, which may provide a new therapeutic strategy for the treatment of adriamycin-induced DCM.

// Sheng Wang 1 , Xuan Zhang 1 , Yuanyuan Guo 1 , Han Rong 1 , Tiebang Liu 1 1 Shenzhen Key Laboratory for Psychological Healthcare, Shenzhen Institute of Mental Health, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, P. R. China Correspondence to: Tiebang Liu, email: minglch13@yeah.net Keywords: Parkinson’s disease, long non-coding RNA, HOTAIR, MPTP, LRRK2 Received: November 22, 2016 Accepted: January 22, 2017 Published: February 19, 2017 ABSTRACT Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes. HOTAIR (Hox transcript antisense intergenic RNA), an approximately 2.2 kb long noncoding RNA transcribed from the HOXC locus, is upregulated in various diseases. However, the role of HOTAIR in Parkinson's disease (PD) remains unclear. A mouse model of PD was developed by intraperitoneal injection of MPTP. The expression of HOTAIR and LRRK2 were detected in the PD mice and in human neuroblastoma cell lines SH-SY5Y pretreated with MPP+. The effect of HOTAIR on the expression of LRRK2 was examined in SH-SY5Y cells through overexpressing or knockdown of HOTAIR. MTT and flow cytometry assay were performed to measure the cell viability and apoptosis of SH-SY5Y cells. We found that HOTAIR was up-regulated in midbrain tissue of MTPT induced PD mice and in SH-SY5Y cells exposed to MPP+. With the presence of HOTAIR overexpression in SH-SY5Y cells, the expression of LRRK2 was increased compared with that in the control. HOTAIR knockdown showed a protective effect on the cell viability of SH-SY5Y cells pretreated with MPP+. HOTAIR knockdown provided protection against MPP+-induced DA neuronal apoptosis by repressing caspase 3 activity. The finding that HOTAIR promoted PD induced by MPTP could add our understanding of the molecular mechanisms in PD. These findings suggested that inhibition of HOTAIR levels is an effective disease-modifying strategy in PD.

// Soo Hee Kim 1, 2 , Se Hoon Kim 1 , Woo Ick Yang 1 , Soo Jeong Kim 3 and Sun Och Yoon 1 1 Department of Pathology, Yonsei University College of Medicine, Seoul, Korea 2 Anatomic Pathology Reference Lab, Seegene Medical Foundation, Seoul, Korea 3 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Correspondence to: Sun Och Yoon, email: soyoon@yuhs.ac , revita@naver.com Keywords: T and NK cell lymphomas, long non-coding RNA, MALAT1, polycomb repressive complex Received: June 13 2016 Accepted: January 31, 2017 Published: February 17, 2017 ABSTRACT Recently, various long non-coding RNAs (lncRNAs) have been reported to have significant therapeutic or prognostic value. However, the expression of lncRNAs has not been investigated in T and NK cell lymphoma. Thus, we evaluated the biological and prognostic role of lncRNAs related to the polycomb repressive complex (PRC) and PRC markers in tissue samples and cell lines of T and NK cell lymphoma. Among the tested lncRNAs, MALAT1 was most highly expressed in clinical samples and cell lines. High expression of MALAT1 as well as BMI1 was related to poor prognosis in patients with mature T cell lymphoma. In the tissue samples, BMI1 expression showed a positive correlation with EZH2, SUZ12, H3K27me3, and MALAT1. Multiple linear regression analysis showed that BMI1 expression was independently associated with H3K27me3. Direct binding of MALAT1 to the PRC2 components (EZH2 and SUZ12) was observed in a T cell lymphoma cell line; however, no direct binding of MALAT1 with H3K27me3 and BMI1 (a PRC1 component) was observed. In T and NK cell lymphomas, MALAT1 was related to poor prognosis. MALAT1 directly binds to EZH2 and SUZ12, and BMI1 activation may be induced possibly through H3K27me3.

// Fei Xie 1, * , Xudong Xiang 2, * , Qionglin Huang 1, * , Pengzhan Ran 1 , Yuncang Yuan 1 , Qian Li 1 , Guoxiang Qi 1 , Xiaopeng Guo 1 , Chunjie Xiao 1, ** , Shangyong Zheng 1, ** 1 School of Medicine, Yunnan University, Kunming, Yunnan 650091, P.R. China 2 Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China * These authors have contributed equally to this work ** These two authors are co-corresponding authors Correspondence to: Chunjie Xiao, email: chjxiao@ynu.edu.cn Shangyong Zheng, email: shangyong@ynu.edu.cn Keywords: long non-coding RNA, lncRNA-BCAT1, β-catenin, tumor suppressor, colorectal cancer Received: September 23, 2016 Accepted: December 27, 2016 Published: February 17, 2017 ABSTRACT β-catenin plays a major role in tumor development and progression. The present study found that β-catenin was upregulated in 30 samples of colorectal cancer (CRC) tissue as compared to adjacent non-tumor tissues. Analysis of long non-coding RNA (lncRNA) expression profiles using the GSE18560 and GSE44097 datasets, which were generated via the Affymetrix plus 2.0 microarray platform and downloaded from the GEO database, revealed 20 differentially expressed lncRNAs following β-catenin knockdown. We focused on AK091631, a novel lncRNA, which we named lncRNA-β-catenin associated transcript 1 (LncRNA-BCAT1). lncRNA-BCAT1 expression was decreased in CRC tissues, and was negatively associated with β-catenin in both CRC tissues and cell lines. lncRNA-BCAT1 overexpression suppressed CRC cell growth and invasion by downregulating cyclin D1, c-Myc, and MMP-2. These results suggest that lncRNA-BCAT1 overexpression inhibits CRC cell growth and invasion via Wnt/β-catenin pathway blockade, and that lncRNA-BCAT1 is repressed by Wnt/β-catenin signaling. This evidence suggests that lncRNA-BCAT1 is a tumor suppressor and that lncRNA-BCAT1 may be an effective prognostic biomarker in CRC.

// Rupeng Zhang 1, 4, 5 , Yuenan Guo 1, 4, 5 , Zhenchi Ma 1, 4, 5 , Gang Ma 2, 4, 5 , Qiang Xue 1, 4, 5 , Fangxuan Li 3, 4, 5 , Liren Liu 2, 4, 5 1 Department of Gastric Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 2 Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 3 Department of Cancer Prevention Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 4 National Clinical Research Center of Cancer, Tianjin 300060, China 5 Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China Correspondence to: Rupeng Zhang, email: tijzhangrp@163.com Liren Liu, email: liuliren@tjmuch.com Keywords: PTENP1, miR-106b, miR-93, long non-coding RNA, gastric cancer Received: October 20, 2016 Accepted: January 29, 2017 Published: February 13, 2017 ABSTRACT Recent studies have shown that competing endogenous RNAs (ceRNAs) play an important role in the regulation of gene expression, and participate in a wide range of biological processes, including carcinogenesis. Long non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, has been reported to exert its tumor suppressive function via modulation of PTEN expression in many malignancies. However, whether a PTENP1~miRNA~PTEN ceRNA network exists and how it functions in gastric cancer (GC) remains elusive. In order to identify and characterize the PTENP1~miRNA~PTEN ceRNA network in GC, we first determined PTENP1 levels in clinical GC samples and found that PTENP1 and PTEN were concurrently downregulated in these samples. We further demonstrated that PTENP1 could act as a ceRNA to sponge miR-106b and miR-93 from targeting PTEN for downregulation using a novel ceRNA in vitro gradient assay. Thus, we revealed a tumor suppressive role of PTENP1 as ceRNA in GC and pinpointed the specific miRNAs decoyed by PTENP1, highlighting the emerging roles of ceRNAs in the biological regulation of GC cells and their possible clinical significance.

// Yang Jin 1, 3 , Zilian Cui 2, 3 , Xudong Li 4 , Xunbo Jin 3 , Jian Peng 1 1 Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China 2 Shandong University School of Medicine, Jinan, Shandong, China 3 Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China 4 Department of Urology, Binzhou People's Hospital, Binzhou, Shandong, China Correspondence to: Zilian Cui, email: 122526195@qq.com Keywords: PlncRNA-1, long noncoding RNA, LNCAP, C4-2, TGF-β1 Received: October 19, 2016 Accepted: January 29, 2017 Published: February 13, 2017 ABSTRACT Objective: To confirm that PlncRNA-1 regulates the cell cycle in prostate cancer cells and induces epithelial-mesenchymal transition (EMT) in prostate cancer through the TGF-β1 pathway. Results: PlncRNA-1 and TGF-β1 expression levels were significantly higher in prostate cancer tissues than in normal prostate tissues ( P < 0.05) and were significantly positively correlated. TGF-β1, N-cadherin and Cyclin-D1 were downregulated and E-Cadherin was upregulated in LNCAP cells after silencing of PlncRNA-1, as determined by real-time PCR and Western blot. TGF-β1, N-cadherin and Cyclin-D1 were upregulated and E-cadherin was downregulated in C4-2 cells, as determined by real-time PCR and Western blot. Overexpression of PlncRNA-1 in C4-2 cells was observed when TGF-β1 inhibitor LY2109761 was added. Western blot analysis showed that compared with their expression when TGF-β1 inhibitor LY2109761 was not added, N-Cadherin and CyclinD1 expression decreased and E-Cadherin expression increased. Transwell results showed that the invasive ability of C4-2 cells was enhanced after overexpression of PlncRNA-1, and the invasion ability was decreased after addition of TGF-β1 inhibitor LY2109761. The cell cycle was blocked by overexpression of PlncRNA-1 in C4-2 and by the addition of TGF-β1 inhibitor LY2109761, as determined by flow cytometry. In vitro experiments showed that PlncRNA-1 can regulate the growth of prostate cancer cells and EMT through the TGF-β1 pathway. In vivo experiments also confirmed the above results. Tumor growth was significantly blocked by overexpressing PlncRNA-1 in C4-2 cells and by the TGF-β1 inhibitor LY2109761 in animal experiments. Materials and Methods: The expression levels of PlncRNA-1 and TGF-β1 were analyzed in 19 prostate cancer tissue samples and in adjacent normal tissue samples, 4 Pca cell lines, including LNCaP, C4-2,DU145, and PC3, and 1 normal prostate epithelial cell line RWPE-1. LNCAP cells were divided into the LNCAP control group and the LNCAP-PlncRNA-1-siRNA group. Cells from the prostate cancer cell line C4-2 were divided into the C4-2 control group and the C4-2-PlncRNA-1 experimental group. Changes in TGF-β1, E-cadherin and N-cadherin were detected by qPCR and Western Blot assay after silencing and overexpression of PlncRNA-1. The cell cycle, cell invasion, and levels of Cyclin-D1, E-Cadherin, and N-Cadherin were observed after adding TGF-β1 inhibitor LY2109761 in the C4-2-PlncRNA-1 group. The effects of TGF-β1 inhibitor LY2109761 on the tumorigenicity of C4-2 cells after overexpression of PlncRNA-1 was investigated in vivo . Conclusions: PlncRNA-1 is an oncogene that regulates the cell cycle, cyclin-D1 and EMT in prostate cancer cells through the TGF-β1 pathway.

// Lu Lu 1, 2, * , Hong Qi 1, 2, * , Fei Luo 1, 2 , Hui Xu 1, 2 , Min Ling 3 , Yu Qin 3 , Ping Yang 4 , Xinlu Liu 1, 2 , Qianlei Yang 1, 2 , Junchao Xue 1, 2 , Chao Chen 1, 2 , Jiachun Lu 4 , Quanyong Xiang 3 , Qizhan Liu 1, 2 , Qian Bian 3 1 Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People’s Republic of China 2 The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People’s Republic of China 3 Jiangsu Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, People's Republic China 4 The School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 510182, Guangdong, People's Republic China * These authors contributed equally to this work Correspondence to: Qizhan Liu, email: drqzliu@hotmail.com Qian Bian, email: bianqian@jscdc.cn Keywords: cigarette smoke extract (CSE), carcinogenesis, miRNAs, lncRNAs, lung cancer Received: November 11, 2016 Accepted: January 09, 2017 Published: February 08, 2017 ABSTRACT Cigarette smoking is a primary risk factor for the development of lung cancer, which is regarded as the leading cause of cancer-related deaths. The process of malignant transformation of cells, however, is complex and elusive. The present study investigated the roles of an lncRNA, CCAT1, and a transcriptional factor, c-Myc, in human bronchial epithelial (HBE) cell transformation induced by cigarette smoke extract. With acute and chronic treatment of HBE cells, cigarette smoke extract induced increases of CCAT1 and c-Myc levels and decreases of levels of let-7c, a microRNA. Down-regulation of c-Myc reduced the degree of malignancy and the invasion/migration capacity of HBE cells transformed by cigarette smoke extract. ChIP assays established that c-Myc, increased by cigarette smoke extract, binds to the promoter of CCAT1, activating its transcription. Further, let-7c suppressed the expression of c-Myc through binding to its 3’-UTR. In turn, CCAT1 promoted the accumulation of c-Myc through binding to let-7c and decreasing free let-7c, which influenced the neoplastic capacity of HBE cells transformed by cigarette smoke extract. These results indicate that a positive feedback loop ensures expression of cigarette smoke extract-induced CCAT1 and c-Myc via let-7c, which is involved in cigarette smoke extract-induced malignant transformation of HBE cells. Thus, the present research establishes a new mechanism for the reciprocal regulation between CCAT1 and c-Myc and provides an understanding of cigarette smoke extract-induced lung carcinogenesis.

// Jia Shi 1,* , Bo Dong 1,* , Jiachao Cao 1,* , Yumin Mao 1 , Wei Guan 1 , Ya Peng 1 and Suinuan Wang 1 1 Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China * These authors have contributed equally to this work Correspondence to: Suinuan Wang, email: // Ya Peng, email: // Keywords : long non-coding RNAs, glioma, microRNA Received : November 11, 2016 Accepted : January 24, 2017 Published : February 07, 2017 Abstract Glioma is regarded as the most prevalent malignant carcinoma of the central nervous system. Thus, the development of new therapeutic strategies targeting glioma is of significant clinical importance. Long non-coding RNAs (lncRNAs) are functional RNA molecules without a protein-coding function and are reportedly involved in the initiation and progression of glioma. Dysregulation of lncRNAs in glioma is due to activation of several signaling pathways, such as the BRD4-HOTAIR-β-catenin/PDCD4, p53-Hif-H19/IGF2 and CRNDE/mTOR pathways. Furthermore, microRNAs (miRNAs) such as miR-675 also interact with lncRNAs in glioma. Thus, exploring the mechanisms by which lncRNA control processes will be instrumental for devising new effective therapies against glioma.

// Hong Li 1, * , Qiong Wu 1, * , Ting Li 1 , Changhao Liu 1 , Lin Xue 1 , Jie Ding 1 , Yongquan Shi 1 , Daiming Fan 1 1 State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China * These authors contributed equally to this work Correspondence to: Qiong Wu, email: fengling00909@163.com Yongquan Shi, email: shiyquan@fmmu.edu.cn Keywords: miR-17-92, circulating miRNA, intestinal metaplasia, gastric cancer, early diagnosis Received: August 12, 2016 Accepted: January 19, 2017 Published: February 02, 2017 ABSTRACT Purpose: Intestinal metaplasia is considered to be a pre-cancerous lesion of gastric cancer. The miR-17-92 cluster was previously reported to have clinical value in the prediction of cancer development. This study aimed to test the diagnostic value of miR-17-92 in gastric cancer and the intestinal metaplasia patients compared with the normal ones. Results: The results showed that miR-17-92 members were over-expressed in the serum of both gastric cancer and intestinal metaplasia patients, compared with healthy controls. Serum miR-17-92 members could also distinguish patients with gastric cancer and intestinal metaplasia from healthy controls. Materials and Methods: Serum miR-17-92 expression levels were detected using quantitative real-time PCR in 75 patients with gastric cancer, 104 patients with intestinal metaplasia and 38 healthy controls. The Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were then analyzed to test the efficacy of the miR-17-92 members in distinguishing gastric cancer, intestinal metaplasia and healthy controls. Conclusions: In conclusion, the miR-17-92 cluster might be useful as a potential serum biomarker for the early detection of gastric cancer.

Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. They have emerged as key players in the pathology of several tumors, including hepatoblastoma. In this study, we elucidate the biological and clinical significance of CRNDE up-regulation in hepatoblastoma. CRNDE is significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. CRNDE knockdown reduces tumor growth and tumor angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, and angiogenic effect in vitro. Mechanistic studies show that CRNDE knockdown plays its anti-proliferation and anti-angiogenesis role via regulating mammalian target of rapamycin (mTOR) signaling. Taken together, this study reveals a crucial role of CRNDE in the pathology of hepatoblastoma. CRNDE may serve as a promising diagnostic marker and therapeutic target for hepatoblastoma.