Search

Temperature is an important environmental factor affecting heading date of rice. Despite its importance, genes responsible for temperature-sensitive heading in rice have remained elusive. Our previous study identified a quantitative trait locus qHd1 which advances heading date under high temperatures. A 9.5-kb insertion was found in the first intron of OsMADS51 in indica variety Zhenshan 97 (ZS97). However, the function of this natural variant in controlling temperature sensitivity has not been verified. In this study, we used CRISPR/Cas9 to knock out the 9.5-kb insertion in ZS97. Experiments conducted under cotrolled conditions in phytotrons confirmed that deletion increased temperature sensitivity and advanced heading by downregulating the expression level of OsMADS51. One-hybrid assays in yeast, ChIP-quantitative polymerase chain reaction, electrophoretic mobility shift, and luciferase-based transient transactivation assays collectively confirmed that OsMADS51 affects heading date by regulation of heading date gene Ehd1. We further determined that the long non-coding RNA HEATINR is generated from the first intron of OsMADS51, offering an explanation for how the 9.5-kb insertion affects temperature sensitivity. We also found that OsMADS51 was strongly selected in early/late-season rice varieties in South China, possibly accounting for their strong temperature sensitivity. These insights not only advance our understanding of the molecular mechanisms underlying the temperature-responsive regulation of heading date in rice but also provide a valuable genetic target for molecular breeding. [ABSTRACT FROM AUTHOR]

Introduction: Immune thrombocytopenia (ITP) is a common acquired hemorrhagic disease without "gold standard" for the diagnosis, long non‐coding RNA (lncRNAs) can participate in regulating gene expression through various mechanisms and may play a role in immune intolerance in ITP. Several previous studies have confirmed that lncRNA lncDC and THRIL are involved in the development of autoimmune diseases. This study investigates the relationship between expression levels of two plasma lncRNAs (lncDC and THRIL) and clinical characteristics of adult primary ITP patients, ascertain their potential applications as diagnostic markers of ITP. Methods: We recruited 102 subjects, including 41 ITP patients, 41 healthy controls (HCs) and 20 patients under myelosuppression phase after chemotherapy (MS). qRT‐PCR was used to detect the expression of two lncRNAs in the peripheral blood plasma of the three groups. Receiver operating characteristic (ROC) curves were used to test the diagnostic efficacy of lncDC and THRIL in ITP. Results: The expression level of lncDC was downregulated in ITP patients compared with HCs (p =. 012) and MS (p =.035), whereas THRIL was significantly upregulated (p =.0005, p <. 0001). We further revealed that lncDC has a high sensitivity (78. 05%), while THRIL has a high specificity (97. 56%). The area under the curve (AUC) (0.869, 95% CI: 0.795–0.943, p <.0001) of the ROC curve for this combination increased significantly. Conclusions: THRIL and lncDC expression levels were changed in adult ITP patients. The lncRNAs lncDC and THRIL can serve as potential diagnostic markers for adult primary ITP. [ABSTRACT FROM AUTHOR]

Background: Oriental river prawn (Macrobrachium nipponense) is one of the most dominant species in shrimp farming in China, which is a rich source of protein and contributes to a significant impact on the quality of human life. Thus, more complete and accurate annotation of gene models are important for the breeding research of oriental river prawn. Results: A full-length transcriptome of oriental river prawn muscle was obtained using the PacBio Sequel platform. Then, 37.99 Gb of subreads were sequenced, including 584,498 circular consensus sequences, among which 512,216 were full length non-chimeric sequences. After Illumina-based correction of long PacBio reads, 6,599 error-corrected isoforms were identified. Transcriptome structural analysis revealed 2,263 and 2,555 alternative splicing (AS) events and alternative polyadenylation (APA) sites, respectively. In total, 620 novel genes (NGs), 197 putative transcription factors (TFs), and 291 novel long non-coding RNAs (lncRNAs) were identified. Conclusions: In summary, this study offers novel insights into the transcriptome complexity and diversity of this prawn species, and provides valuable information for understanding the genomic structure and improving the draft genome annotation of oriental river prawn. [ABSTRACT FROM AUTHOR]

Phyllostachys edulis (moso bamboo) is China's most widespread bamboo species, with significant economic and ecological values. Long non-coding RNA (lncRNA) is a type of regulatory RNA that is longer than 200 nucleotides and incapable of encoding proteins, and is frequently involved in regulating biotic and abiotic stress and plant development. However, the biological functions of lncRNA in moso bamboo are unknown. In this study, a lncRNA (named PelncRNA1) differentially expressed following UV-B treatment was discovered in the whole transcriptome sequencing database of moso bamboo. The target genes were filtered and defined by correlation analysis of PelncRNA1 and gene expression pattern. The expression levels of PelncRNA1 and its target genes were verified using qRT-PCR. The results demonstrated that the expression levels of PelncRNA1 and its target genes increased during UV-B treatment. In Arabidopsis transgenic seedlings and moso bamboo protoplasts, PelncRNA1 was discovered to influence the expression of its target genes when overexpressed. In addition, transgenic Arabidopsis showed higher tolerance to UV-B stress. These results suggest that PelncRNA1 and its target genes are involved in the response of moso bamboo to UV-B stress. The novel findings would contribute to our understanding of how lncRNAs regulate the response to abiotic stresses in moso bamboo. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are a kind of non-coding RNA being >200 nucleotides in length, and they are found to participate in hair follicle growth and development and wool fiber traits regulation. However, there are limited studies reporting the role of lncRNAs in cashmere fiber production in cashmere goats. In this study, Liaoning cashmere (LC) goats (n = 6) and Ziwuling black (ZB) goats (n = 6) with remarkable divergences in cashmere yield, cashmere fiber diameter, and cashmere color were selected for the construction of expression profiles of lncRNAs in skin tissue using RNA sequencing (RNA-seq). According to our previous report about the expression profiles of mRNAs originated from the same skin tissue as those used in the study, the cis and trans target genes of differentially expressed lncRNAs between the two caprine breeds were screened, resulting in a lncRNA–mRNA network. A total of 129 lncRNAs were differentially expressed in caprine skin tissue samples between LC goats and ZB goats. The presence of 2 cis target genes and 48 trans target genes for the differentially expressed lncRNAs resulted in 2 lncRNA-cis target gene pairs and 93 lncRNA-trans target gene pairs. The target genes concentrated on signaling pathways that were related to fiber follicle development, cashmere fiber diameter, and cashmere fiber color, including PPAR signaling pathway, metabolic pathways, fatty acid metabolism, fatty acid biosynthesis, tyrosine metabolism, and melanogenesis. A lncRNA–mRNA network revealed 22 lncRNA-trans target gene pairs for seven differentially expressed lncRNAs selected, of which 13 trans target genes contributed to regulation of cashmere fiber diameter, while nine trans target genes were responsible for cashmere fiber color. This study brings a clear explanation about the influences of lncRNAs over cashmere fiber traits in cashmere goats. [ABSTRACT FROM AUTHOR]

Diabetic wounds are a protracted complication of diabetes mainly characterised by chronic inflammation, obstruction of epithelialization, damaged blood vessels and collagen production (maturation), as well as neuropathy. As a non‐coding RNA (ncRNA) that lack coding potential, long non‐coding RNAs (lncRNAs) have recently been reported to play a salient role in diabetic wound healing. Here, this review summarises the roles of lncRNAs in the pathology and treatments of diabetic wounds, providing references for its potential clinical diagnostic criteria or therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

The leaf and the flower are vital plant organs owing to their roles in photosynthesis and reproduction. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and transcription factors (TFs) are very important to the development of these organs. Liriodendron chinense is a common ornamental tree species in southern China with an unusual leaf shape and tulip-like flowers. The genetic mechanisms underlying leaf and flower development in L. chinense and the miRNA-lncRNA-TF regulatory networks are poorly studied. Through the integration and analysis of different types of sequencing data, we identified the miRNA-lncRNA-TF regulatory networks that were related to leaf and flower development. These networks contained 105 miRNAs, 258 lncRNAs, 393 TFs, and 22 endogenous target mimics. Notably, lch-lnc7374-miR156h- SPL3 and lch-lnc7374-miR156j- SPL9 were potential regulators of stamen and pistil development in L. chinense , respectively. miRNA-lncRNA-mRNA regulatory networks were shown to impact anther development, male and female fertility, and petal color by regulating the biosynthesis of phenylpropanoid metabolites. Phenylpropanoid metabolite biosynthesis genes and TFs that were targeted by miRNAs and lncRNAs were differentially expressed in the leaf and flower. Moreover, RT-qPCR analysis confirmed 22 differentially expressed miRNAs, among which most of them showed obvious leaf or flower specificity; miR157a- SPL and miR160a- ARF module were verified by using RLM-RACE, and these two modules were related to leaf and flower development. These findings provide insight into the roles of miRNA-lncRNA-mRNA regulatory networks in organ development and function in L. chinense , and will facilitate further investigation into the regulatory mechanisms of leaf and flower development in L. chinense. [ABSTRACT FROM AUTHOR]

Schizothorax prenanti (S. prenanti) is one of the most important aquaculture species in the southwest of China. However, information of the full-length transcripts in S. prenanti remains unknown. In this study, single-molecule real-time (SMRT) sequencing was performed to generate full-length transcriptomes of S.prenanti. In total, 23.26 Gb of clean reads were generated. A total of 312,587 circular consensus sequences (CCS) were obtained with average lengths of 2634 bp and 84.16% (270,662) of CCS were full-length non-chimeric reads. After being corrected with Illumina library sequencing, 18,005 contigs were obtained, with 17,797 (98.81%) successfully annotated in eight public databases, including 15,839 complete open reading frames (ORFs) with an average length of 1330 bp. Furthermore, a total of 4152 alternative splicing (AS) events and 250 long non-coding RNA (lncRNA) transcripts were detected. Additionally, a total of 1129 putative transcription factors (TFs) members from 56 TF families and 11,660 simple sequence repeats (SSRs) were identified. This study provided a valuable resource of full-length transcripts for further research on S. prenanti. • A total of 18,005 unigenes were obtained, including 15,839 complete ORFs. • A total of 341 alternative splicing (AS) events and 250 long non-coding RNA (lncRNA) transcripts were detected. • In total, 1129 putative transcription factors (TFs) members from 56 TF families and 11,660 simple sequence repeats (SSRs) were identified. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China. As an important participant in tumor biology, the abnormal expression of long non-coding RNA (lncRNAs) in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor genes. In this study, we identified a novel lncRNA NFIA antisense RNA 1 (NFIA-AS1) and explored its role and clinical significance in gastric cancer. Real-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer samples. The lower expression of NFIA-AS1 was significantly associated with larger tumor size, lower histological grade, and advanced TNM stage. Kaplan-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall survival. We also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 levels. In conclusion, our results suggest that the lncRNA NFIA-AS1 may play the role of tumor suppressor gene, and serve as a biomarker for prognosis or progression of gastric cancer. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the malignant tumors with the highest incidence and mortality rate in China, and its occurrence and development mechanism and treatment methods are the current research focuses. In recent years, the emergence of drugs targeting various tumor driver genes has significantly improved patients' survival and quality of life, setting off a wave of research on new therapeutic targets. Among them, long non-coding RNA (lncRNA) plays a crucial role in the malignant behavior of tumors, which has attracted widespread attention. Shown by a large number of studies, partial members of lncRNA small nucleolar RNA host gene (SNHG) family are aberrantly expressed in many maliglant tumors including non-small cell lung cancer (NSCLC) and participate in cell proliferation, invasion and migration, which may act as a new diagnostic and prognostic biomarker and can be a therapeutic target of NSCLC. In this review, we comprehensively summarize and explore the recent investigation of SNHGs in NSCLC in order to provide new ideas for the diagnosis and treatment of NSCLC.
.

Microarray expression profiles of lncRNAs and mRNAs were investigated in HepG2 cells treated with 20 μg/ml ginsenoside Rh2 as well as in ginsenoside Rh2-untreated cells. Microarray analysis showed 618 upregulated lncRNAs and 161 downregulated lncRNAs in HepG2 cells treated with ginsenoside Rh2 compared with the control group. Moreover, three differentially expressed lncRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). This may be beneficial to patients as an anti-cancer treatment and potentially provide novel targets for HCC (hepatocellular carcinoma) therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Long non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer. Objective We sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC). Design, setting, and participants Based on the RNA-seq data of 444 stage I–III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I–III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I–III ccRCC. Outcome measurements and statistical analysis Univariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival. Results and limitations Using the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03–1.75; p = 0.028] to 1.89 [95% CI, 1.55–2.31; p < 0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II–III patients. Conclusions The RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I–III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management. Patient summary The RCClnc4 classifier could facilitate patient management and treatment decisions. Take Home Message Our RCClnc4 classifier could add prognostic value to existing clinicopathological risk factors for stage I–III clear cell renal cell carcinoma and provide a more accurate and individualized risk assessment beyond reported signature. The RCClnc4 classifier may facilitate patient management and treatment decisions. [ABSTRACT FROM AUTHOR]

Cancer has emerged as the most common cause of death in China. The change in lipid metabolism has been confirmed to have a role in several tumor types, such as esophageal, gastric, colorectal and liver cancer. Cancer cells use lipid metabolism for energy and then rapidly proliferate, invade and migrate. The main pathway by which cancer cell lipid metabolism influences cancer progression is increased fatty acid synthesis. Long non-coding (lnc)RNAs are important ncRNAs that were indicated to have significant roles in the development of human tumors. They are considered potential tumor biomarkers. Increased lipid synthesis or uptake due to deregulation of lncRNAs contributes to rapid tumor growth. In the present review, current studies on the relationship between lncRNAs, lipid metabolism and the occurrence and development of tumors were collated and summarized, and their mechanism of action was discussed. The review is expected to provide a theoretical basis for tumor treatment and prognosis evaluation based on the effective regulation of lncRNAs and lipid metabolism. [ABSTRACT FROM AUTHOR]

Aim To screen and validate the gastric cancer-associated long non-coding RNAs (lncRNAs) and their functional single nucleotide polymorphisms (SNPs). Methods Based on case-control design, we select the differentially expressed lncRNAs by bioinformation tools and validate SNPs in lncRNAs genes in population. Attributable risk percentage ( ARP ) and population attributable risk percentage ( PARP ) were used to assess the effect of epidemiology. Results Four lncRNAs with SNPs ( lnc-EVX1-3:3 (rs1859168), lnc-MACC1-1:7 (rs3815254), lnc-AMFR-1:1 (rs4784659) and lnc-ZNF33B-2:1 (rs579501)) were selected to be validated in population. The unconditional multiple logistic regression based on the dominant (odds ratio, OR = 0.64, 95%confidence interval, 95%CI: 0.47–0.86) and recessive genetic model ( OR = 1.77, 95%CI: 1.34–2.35) showed rs1859168 was significantly associated with lower risk of gastric cancer. The dominant ( OR = 0.42, 95%CI:0.31–0.57) and additive ( OR = 0.52, 95%CI:0.40–0.67) genetic model revealed that rs4784659 decreased the risk of gastric cancer. Similarly, the dominant ( OR = 0.72, 95%CI: 0.52–0.98) and additive ( OR = 0.73, 95%CI: 0.56–0.97) genetic model showed the individuals with rs579501 had reduced risk of gastric cancer. Whereas no statistical association between rs3815254 and gastric cancer. ARP and PARP for gastric cancer associated with rs1859168 in dominant model (56.25%, 33.05%), and in recessive model (43.50% and 29.37%). For rs4784659, ARP and PARP were 138.09% and 10.39% in dominant model, 92.31% and 8.76% in additive model. For rs579501, ARP and PARP were 38.89% and 4.03% in dominant model, 36.99% and 3.88% in additive model. Conclusion Our findings showed rs4784659, rs579501 and rs1859168 reduced the susceptibility of gastric cancer. From epidemiological perspective, the lncRNAs with SNPs attenuate the development of gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: To monitor the expression of long non-coding RNAs (lncRNAs) and changes in metabolic profiles among patients with gestational diabetes mellitus (GDM).Methods: A retrospective case-control study was conducted using data for women treated at a hospital in China between October 8, 2014, and April 15, 2015. Patients diagnosed with GDM using an oral glucose tolerance test at 24-28 weeks of pregnancy (n=50) were included. The control group comprised pregnant women without GDM (n=47). Serum levels of lncRNA MALAT1, lncRNA p21, and lncRNA H19 were assessed using the reverse transcription polymerase chain reaction. Plasma glucose and lipid levels were assessed biochemically.Results: The expression level of lncRNA MALAT1 was higher among the cases than the controls (P=0.007). Expression of IncRNA MALAT1 among the patients with GDM correlated with both lncRNA p21 (r=0.333, P=0.018) and lncRNA H19 (r=0.314, P=0.030). Levels of triglycerides and total cholesterol differed between the control group and patients with GDM (3.6 ± 2.6 mmol/L vs 3.8 ± 1.5 mmol/L and 6.54 ± 1.30 mmol/L vs 7.40 ± 0.90 mmol/L, respectively; P<0.05). The area under the receiver operating characteristic curve was 0.654 (95% confidence interval 0.543-0.768, P<0.001).Conclusion: Expression of lncRNA MALAT1 could offer a novel biomarker to predict GDM. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is a chronic, lifelong disease. The molecular mechanisms and pathophysiology of T2DM have not yet been fully elucidated. Dysregulation of the long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) is considered one of the main contributing factors of the dysfunction found in many diseases, including those of the endocrine system. The aim of this study was to investigate the association between lncRNA MALAT1 single nucleotide polymorphisms (SNPs) and T2DM in the Chinese Han population., Methods: We genotyped three SNPs (rs3200401 C > T, rs619586 A > G, rs11227209 C > G) of the MALAT1 gene, including 571 T2DM patients and 526 controls. The association between different genotypes and the risk of T2DM was analyzed using logistic regression, and the results were expressed by odds ratio (OR) and its 95% confidence interval (95%CI), and then stratified by age, sex, and BMI. P < 0.05 on both sides was considered as statistically significant., Results: We found that the CT + TT genotypes of the rs3200401 polymorphism were significantly associated with an increased risk of T2DM in Chinese Han population (OR = 1.77; 95% CI:1.35-2.33; P adjusted  < 0.001), whereas MALAT1 rs619586 AG + GG genotypes were associated with a reduced risk of T2DM (OR = 0.67; 95% CI:0.48-0.94; P adjusted  = 0.021). Subsequent stratified analysis showed that compared with the rs3200401 CC genotype, CT + TT genotypes were associated with an increased risk of T2DM in the male, female, age ≥ 65 years, and BMI ≥ 24 subgroups (OR = 1.68, 95% CI:1.10-2.56, P adjusted  = 0.016; OR = 1.83, 95% CI:1.27-2.62, P adjusted  = 0.001; OR = 1.86, 95% CI:1.38-2.52, P adjusted  < 0.001; OR = 2.13, 95% CI:1.45-3.15, P adjusted  < 0.001; respectively). Haplotype analysis showed that T-A-C haplotype had a 1.533-fold increased risk of T2DM (95% CI, 1.208-1.945, P < 0.001) and C-G-G was associated with a decreased risk of T2DM. No significant association was found between rs11227209 and T2DM risk (P > 0.05)., Conclusion: The results suggest that MALAT1 rs619586 and rs3200401 confer susceptibility for T2DM in the Chinese Han population and provide new genetic targets for the treatment of diabetes and its complications in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Accumulating evidence suggested that long non-coding RNAs (lncRNAs) could play biological roles in cardiovascular diseases. We investigated whether lncRNAs can serve as biomarkers for salt sensitivity of blood pressure (SSBP). Participants were divided into salt-sensitive (SS) and salt-resistant (SR) ones by oral saline test. LncRNAs were tested by microarray (N = 20) and two-stage qRT-PCR (N = 89 and 228). We identified five differently expressed lncRNAs (lnc-IGSF3-1:1, SCOC-AS1, SLC8A1-AS1, KCNQ1OT1, and lnc-GNG-10-3:1) between SS and SR. In single-lncRNA analyses, lnc-IGSF3-1:1 displayed better diagnostic performance in hypertensive patients (AUC = 0.840), while SCOC-AS1 in normotensive (AUC = 0.810). In multi-lncRNA analyses, lnc-IGSF3-1:1 + SCOC-AS1 + SLC8A1-AS1 combination showed the best diagnostic performance in hypertensive (AUC = 0.853) and normotensive groups (AUC = 0.873). We constructed a lncRNA-mRNA-GO-KEGG-disease network by bioinformatic analysis; lnc-IGSF3-1:1 and SLC8A1-AS1 were identified as hub biomarkers. Our findings suggest that lnc-IGSF3-1:1, SCOC-AS1, and SLC8A1-AS1 may represent as genetic susceptible biomarkers for SSBP, and had different SS diagnostic performance in hypertensive patients and normotensive individuals., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gastric cancer has been indicated to have a high recurrence rate in China. Previous studies have revealed that long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) exerted critical roles in cancers. Therefore, the present study aimed to determine the function of NEAT1 and explore the unknown molecular mechanisms of gastric cancer pathogenesis. Reverse transcription-quantitative PCR assay was used to examine the expression of NEAT1, microRNA (miR)-142-5p and jagged1 (JAG1) in gastric cancer. Cell Counting Kit-8 and Transwell assays were conducted to examine cell proliferation, migration and invasion. The protein expression levels of N-cadherin, Vimentin, E-cadherin and JAG1 were quantified by western blot assay. The associations among NEAT1, miR-142-5p and JAG1 were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. The effects of NEAT1 silencing on tumor growth were evaluated by tumor xenografts. The results indicated that NEAT1 was highly expressed in tumor tissues and cells compared with that in paracancerous tissues and the normal gastric epithelial cell line GES-1 and significantly associated with poor prognosis in gastric cancer. Functional analyses further demonstrated that NEAT1 knockdown suppressed proliferation, motility and tumor growth in vitro and in vivo. Mechanistically, NEAT1 sponged miR-142-5p to regulate JAG1 expression. In addition, the effects of NEAT1 knockdown on the proliferation, migration and invasion of gastric cancer cells could be rescued by miR-142-5p inhibitor, and JAG1 overexpression reversed the miR-142-5p-mediated effects on gastric cancer cells. These findings demonstrated that long non-coding RNA NEAT1 regulated gastric cancer progression by targeting the miR-142-5p/JAG1 axis. [ABSTRACT FROM AUTHOR]

It is important to determine the mechanism of liver fibrosis for targeted therapy and the development of targeted therapies for liver fibrosis may offer promise for patients with liver disease. Long non‑coding RNAs (lncRNAs) serve a role in hepatic fibrosis. The lncRNA maternally expressed gene 3 (MEG3) has been confirmed to inhibit liver fibrosis. The present study investigated the role of the MEG3 in healthy patients and patients with liver fibrosis. The expression levels of MEG3 and microRNA (miR)‑145 in the serum of healthy volunteers and patients with liver fibrosis and in LX‑2 cells were detected using reverse transcription‑quantitative PCR. A dual‑luciferase reporter assay was used to determine the targeting relationship between MEG3 and miR‑145, and the targeting relationship between miR‑145 and peroxisome proliferator‑activated receptor γ (PPARγ). The protein expression levels of PPARγ, α‑smooth muscle actin (α‑SMA) and collagen I (COL1A1) were detected using western blotting. The expression levels of α‑SMA and COL1A1 were also determined using immunofluorescence. Finally, a Cell Counting Kit‑8 assay was performed to assess the proliferative ability of LX‑2 cells. A significantly reduced MEG3 expression level was demonstrated in serum from patients with liver fibrosis compared with serum from healthy controls. TGF‑β1 induced a significantly decreased MEG3 expression level in LX‑2 human hepatic stellate cells in vitro . The TGF‑β1‑induced increases in cell proliferation and α‑SMA and COL1A1 protein expression levels were reversed following MEG3 overexpression. The results also demonstrated that MEG3 sponged miR‑145 and competed endogenously with miR‑145 to regulate PPARγ. In summary, the present study identified MEG3 as an anti‑fibrotic lncRNA and provided new information regarding the role of MEG3 in liver fibrosis. MEG3 may therefore be a potential target in the treatment of liver fibrosis.

Long non-coding RNAs (lncRNAs) have been reported to play an important role in cardiovascular diseases. The present study aimed to investigate the levels of lncRNA H19 in patients with coronary artery disease (CAD) and the genetic association of lncRNA H19 rs217727 and rs4929984 polymorphisms with CAD susceptibility. We detected an upregulated expression of lncRNA H19 in the peripheral blood of CAD patients compared with healthy controls, and the area under the receiver operating characteristic curve of lncRNA H19 for CAD diagnosis was 0.918. In addition, rs4929984 was associated with the susceptibility of Han Chinese females to CAD, as shown in the additive and dominant models, and the significant association remained after adjusting for age and Bonferroni correction. The A allele carriers of rs4929984 were correlated with females' susceptibility to CAD compared with the C allele, and the A-G haplotype of rs4929984-rs217727 was associated with females' susceptibility to CAD. Furthermore, rs217727 and rs4929984 were associated with the levels of clinicopathological parameters of CAD cases. We suggest that lncRNA H19 has a potential to be a diagnostic biomarker for CAD; rs4929984 polymorphism is associated with females' susceptibility to CAD in the Han Chinese population, and lncRNA H19 variants may influence lipid metabolism, inflammation, and coagulation function of CAD patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale: Most current cardiac regeneration approaches result in very limited cell division and little new cardiomyocyte (CM) mass. Positive feedback loops are vital for cell division, but their role in CM regeneration remains unclear. We aimed to determine whether the lncRNA small nucleolar RNA host gene 1 Snhg1 (Snhg1) could form a positive feedback loop with c-Myc to induce cardiac regeneration. Methods: Quantitative PCR and in situ hybridization experiments were performed to determine the Snhg1 expression patterns in fetal and myocardial infarction (MI) hearts. Gain- and Loss-of-function assays were conducted to explore the effect of Snhg1 on cardiomyocyte (CM) proliferation and cardiac repair following MI. We further constructed CM-specific Snhg1 knockout mice to confirm the proliferative effect exerted by Snhg1 using CRISPR/Cas9 technology. RNA sequencing and RNA pulldown were performed to explore how Snhg1 mediated cardiac regeneration. Chromatin immunoprecipitation and luciferase reporter assays were used to demonstrate the positive feedback loop between Snhg1 and c-Myc. Results: Snhg1 expression was increased in human and mouse fetal and myocardial infarction (MI) hearts, particularly in CMs. Overexpression of Snhg1 promoted CM proliferation, angiogenesis, and inhibited CM apoptosis after myocardial infarction, which further improved post-MI cardiac function. Antagonism of Snhg1 in early postnatal mice inhibited CM proliferation and impaired cardiac repair after MI. Mechanistically, Snhg1 directly bound to phosphatase and tensin homolog (PTEN) and induced PTEN degradation, activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway to promote CM proliferation. The c-Myc protein, one of downstream targets of PI3K/AKT signaling, functioned as a transcription factor by binding to the promoter regions of Snhg1. Perturbation of the positive feedback between Snhg1 and c-Myc by mutation of the binding sequence significantly affected Snhg1-induced CM proliferation. Conclusions: Snhg1 effectively elicited CM proliferation and improved cardiac function post-MI by forming a positive feedback loop with c-Myc to sustain PI3K/Akt signaling activation, and thus may be a promising cardiac regeneration strategy in treating heart failure post-MI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

• LncRNA FAM83H-AS1 was high-expressed in gastric cancer. • FAM83H-AS1 was related with chemotherapy insensitivity in gastric cancer. • Silence of FAM83H-AS1 enhanced the CDDP and 5-FU sensitivity of SGC7901/R cells. • FAM83H-AS1 promotes chemoresistance of gastric cancer through Wnt/β-catenin pathway. Gastric cancer (GC) is a malignant tumor originated from the epithelium of gastric mucosa, its incidence is second only to lung cancer in China. Chemotherapy is one of the most effective methods to treat GC, but some patients are insensitive to chemotherapeutic drugs, leading to chemotherapy failure. In this study, the expression of FAM83H-AS1 was up-regulated in GC tissues and cell lines, and was related to differentiation, invasion depth and chemotherapy insensitivity of GC patients. FAM83H-AS1 was high-expressed in chemoresistant GC tissues and cell line (SGC7901/R), and silence of FAM83H-AS1 sensitized SGC7901/R cells to cisplatin (CDDP) and 5-fluorouracil (5-FU). In addition, silence of FAM83H-AS1 could inactivate Wnt/β-catenin signaling pathway in SGC7901/R cells. The activating of Wnt/β-catenin signaling pathway reversed the promoting effect of FAM83H-AS1 silence on chemotherapy sensitivity, which meant Wnt/β-catenin signaling pathway mediated the regulation of FAM83H-AS1 on chemotherapy sensitivity in SGC7901/R cells. In conclusion, FAM83H-AS1 is related with the CDDP and 5-FU insensitivity of GC patients, silence of FAM83H-AS1 promotes chemosensitivity of GC through Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Aim: This study focused on the expression pattern of long non-coding RNA maternally expressed gene 3 (MEG3) and its value in ischemic stroke (IS)., Methods: The expression pattern and the roles of MEG3 in the development of IS were explored in mice IS model and human brain microvascular endothelial cells (hBMECs). A case-control study, including 215 IS patients and 153 controls, was also conducted to investigate its prognostic value., Results: In vivo study showed that MEG3 increased significantly in the IS group (P=0.004), and its level remained stable within 3 to 48h after the onset of IS. Besides, the survival time of the mouse in the high MEG3 group was significantly lower than that in the low MEG3 group (P=0.042). In vitro study showed that oxygen-glucose deprivation (OGD) treatment significantly up-regulated expressions of MEG3, Bax, and cleaved caspase-3, and further promoted apoptosis of hBMECs, while si-MEG3 blocked these effects. A human study showed that MEG3 increased markedly within 48h of IS onset and was positively associated with the National Institutes of Health Stroke Scale (r=0.347, P＜0.001), modified Rankin Scale (r=0.385, P＜0.001), high-sensitivity C-reactive protein (r=0.221, P=0.002) level, and infarct volume (r=0.201, P=0.006). Overall survival analysis showed that patients with higher MEG3 expression within 48h had a relatively poor prognosis (P＜0.001). Meanwhile, multivariate analysis revealed that MEG3 was an independent prognostic marker for unfavorable functional outcome and death in IS patients., Conclusions: This study suggested that MEG3 might be considered as an intervention point and potential prognostic indicator for IS.

Background: High-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility., Methods: This study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a χ 2 test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models., Results: We observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR=0.65, 95% CI=0.43-0.98, p=0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤32 (codominant model: p=0.006; recessive model: p=0.005 additive model: p=0.018; and allele model: p=0.012; rs72625676, codominant model: p=0.038; recessive model: p=0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p=0.049; recessive model: p=0.029; rs1962430: genotype model: p=0.024; recessive model: p=0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p=0.018)., Conclusion: Our study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

Objective: A new perspective of determining the pathophysiology of systemic lupus erythematosus (SLE) development is required. The current study explores the aberrant expression of long non-coding RNAs (lncRNA), microRNA (miRNA) and mRNA. The study further constructs and analyses the lncRNA-miRNA-mRNA network to elucidate their gene regulation roles in SLE., Method: We extracted mRNA, lncRNA and miRNA from the whole venous blood of 20 SLE patients and 20 normal control (NC) healthy individuals. A lncRNA-mRNA-miRNA network in SLE was constructed using a bioinformatics approach. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database and Cytoscape software to explore the function of mRNAs in this network., Result: A total of 855 mRNA, 7311 lncRNA and 134 miRNA with differentially expressed profiles were identified. Meanwhile, we established a competing endogenous RNA (ceRNA) subnetwork composed of 52 differentially expressed lncRNAs (DElncRNAs), seven differentially expressed miRNAs and 10 differentially expressed mRNAs. We extracted the subnetwork from the ceRNA network and found that three novel miRNAs were key: hsa-miR-145, hsa-miR-17 and hsa-miR-143. We also deduced that the DElncRNAs MIAT and NEAT1 might play crucial roles in the pathogenesis of SLE. The results were verified by bioinformatics analysis., Conclusion: Our results provide a novel perspective for studying lncRNA-related and miRNA-related ceRNA networks in SLE.

Objective: To study the role of long non-coding RNA (lncRNA) LINC00978 in hepatocellular carcinoma (HCC) carcinogenesis., Materials and Methods: LINC00978 expression level was measured by reverse transcription quantitative real-time PCR (RT-qPCR) in HCC tissues and adjacent healthy liver tissues from 49 HCC patients. MTT assay, colony forming assay, and flow cytometry were performed to evaluate the effects of shRNA-mediated LINC00978 knockdown on HCC cell proliferation, cell cycle progression, and apoptosis in vitro. Xenograft tumor model was performed to determine the effects of LINC00978 knockdown on HCC tumor growth in vivo. Western blot was used to assess the activation of signaling molecules in the apoptosis and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway., Results: LINC00978 expression was significantly up-regulated in human HCC tissue relative to adjacent normal tissue, and LINC00978 high expression was correlated with poor HCC overall survival. LINC00978 was up-regulated in HCC cell lines. ShRNA-mediated LINC00978 knockdown significantly decreased HCC cell proliferation, and induced HCC cell cycle arrest and apoptosis in vitro. LINC00978 knockdown led to significant decrease in tumor xenograft size in vivo. Western blots revealed LINC00978 inhibition decreased ERK, p38, and c-Jun N-terminal kinase (JNK) phosphorylation in HCC cells., Conclusions: LINC00978 is highly expressed in human HCC tissue and correlates with poor HCC prognosis. LINC00978 promotes HCC cell proliferation, cell cycle progression, and survival, partially by activating the MAPK/ERK pathway. Our findings partially elucidated the roles of LINC00978 in HCC carcinogenesis, and identified a therapeutic target for HCC., (© 2020 The Author(s).)

Objectives: Tuberculosis (TB) remains a global public health problem. Recent studies have implicated long non-coding RNAs and their variants as possibly playing important roles in TB. The aim of this study was to assess the clinical relevance of lnc-AC145676.2.1-6 and lnc-TGS1-1 and their variants in a western Chinese population., Methods: This case-control study included 467 TB patients and 473 healthy controls from West China Hospital. The expression levels of lnc-AC145676.2.1-6 and lnc-TGS1-1 were analyzed by reverse transcriptase quantitative real-time PCR. Single-nucleotide polymorphism genotyping was performed using a custom-designed 2 × 48-Plex SNPscan kit., Results: It was observed that lnc-AC145676.2.1-6 and lnc-TGS1-1 expression levels were both obviously down-regulated in TB patients. In addition, a lower expression level of lnc-TGS1-1 was associated with the presence of thrombocytopenia in TB patients during anti-TB treatment, and the homozygous CC genotype of rs4737420 correlated with a decreased risk of leukopenia, compared with individuals with the T allele (TT/CT genotype), in the dominant mode., Conclusions: For the first time, potential TB-associated promoting effects were identified for the decreased expression levels of lnc-AC145676.2.1-6 and lnc-TGS-1, while lnc-TGS1-1 and its variant rs4737420 may be predictive indicators of anti-TB drug-induced adverse drug reactions. Larger validation studies on different populations are warranted to confirm these findings., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Glioma is one of the most common types of malignant primary central nervous system tumor, and prognosis for this disease is poor. As autophagic drugs have been reported to induce glioma cell death, we investigated the potential prognostic role of autophagy-associated long non-coding RNA (lncRNA) in glioma patients. In this study, we obtained 879 lncRNAs and 216 autophagy genes from the Chinese Glioma Genome Atlas microarray, and found that 402 lncRNAs are correlated with the autophagy genes. Subsequently, 10 autophagy-associated lncRNAs with prognostic value ( PCBP1-AS1 , TP53TG1 , DHRS4-AS1 , ZNF674-AS1 , GABPB1-AS1 , DDX11-AS1 , SBF2-AS1 , MIR4453HG , MAPKAPK5 -AS1 and COX10-AS1 ) were identified in glioma patients using multivariate Cox regression analyses. A prognostic signature was then established based on these prognostic lncRNAs, dividing patients into low-risk and high-risk groups. The overall survival time was shorter in the high-risk group than that in the low-risk group [hazard ratio (HR) = 5.307, 95% CI: 4.195-8.305; P  < 0.0001]. Gene set enrichment analysis revealed that the gene sets were significantly enriched in cancer-related pathways, including interleukin (IL) 6/Janus kinase/signal transducer and activator of transcription (STAT) 3 signaling, tumor necrosis factor α signaling via nuclear factor κB, IL2/STAT5 signaling, the p53 pathway and the KRAS signaling pathway. The Cancer Genome Atlas dataset was used to validate that high-risk patients have worse survival outcomes than low-risk patients (HR = 1.544, 95% CI: 1.110-2.231; P  = 0.031). In summary, our signature of 10 autophagy-related lncRNAs has prognostic potential for glioma, and these autophagy-related lncRNAs may play a key role in glioma biology., Competing Interests: The authors declare no conflict of interest.

Background: Long non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer., Objective: We sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC)., Design, Setting, and Participants: Based on the RNA-seq data of 444 stage I-III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I-III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I-III ccRCC., Outcome Measurements and Statistical Analysis: Univariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival., Results and Limitations: Using the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03-1.75; p=0.028] to 1.89 [95% CI, 1.55-2.31; p<0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II-III patients., Conclusions: The RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I-III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management., Patient Summary: The RCClnc4 classifier could facilitate patient management and treatment decisions., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The rs2147578 C > G polymorphism in the long non-coding RNA gene Lnc-LAMC2-1:1 is associated with increased susceptibility to a few types of cancers. However, its role in neuroblastoma has not been evaluated yet., Methods: We investigated the association between the lnc-LAMC2-1:1 rs2147578 C > G polymorphism and neuroblastoma susceptibility in Chinese Han populations. A total of 393 neuroblastoma cases and 812 healthy individuals from the Henan and Guangdong provinces were enrolled and subjected to genotyping. Odds ratio (OR) and 95% confidence interval (CI) were used to determine the strength of the association of interest., Results: Combined analysis revealed that the lnc-LAMC2-1:1 rs2147578 C > G polymorphism was associated with increased neuroblastoma susceptibility (CG vs. CC: adjusted OR = 1.33, 95% CI = 1.01-1.75, P = 0.045; CG/GG vs. CC: adjusted OR = 1.34, 95% CI = 1.03-1.74, P = 0.028). In stratification analysis, children under 18 months with rs2147578 CG/GG genotypes had an increased neuroblastoma risk (adjusted OR = 1.70, 95% CI = 1.08-2.67, P = 0.022). Females with rs2147578 CG/GG genotypes also had increased neuroblastoma susceptibility (adjusted OR = 2.08, 95% CI = 1.37-3.18, P = 0.0007). In addition, children with lnc-LAMC2-1:1 rs2147578 CG/GG genotypes were prone to develop earlier stages of neuroblastoma (adjusted OR = 1.46, 95% CI = 1.01-2.12, P = 0.046)., Conclusions: The Lnc-LAMC2-1:1 rs2147578 C > G polymorphism may contribute to increased neuroblastoma susceptibility in children of Henan province.

Aim: To evaluate the association of 12 tag single nucleotide polymorphisms (tagSNPs) in three onco-long non-coding RNA (lncRNA) genes ( HOTTIP , CCAT2 , MALAT1 ) with the risk and prognosis of hepatocellular cancer (HCC)., Methods: Twelve tagSNPs covering the three onco-lncRNAs were genotyped by the KASP method in a total of 1338 samples, including 521 HCC patients and frequency-matched 817 controls. The samples were obtained from an unrelated Chinese population at the First Hospital of China Medical University from 2012-2015. The expression quantitative trait loci (eQTL) analyses were conducted to explore further the potential function of the promising SNPs., Results: Three SNPs in HOTTIP , one promoter SNP in MALAT1 , and one haplotype of HOTTIP were associated with HCC risk. The HOTTIP rs17501292, rs2067087, and rs17427960 SNPs were increased to 1.55-, 1.20-, and 1.18-fold HCC risk under allelic models ( P = 0.012, 0.017 and 0.049, respectively). MALAT1 rs4102217 SNP was increased to a 1.32-fold HCC risk under dominant models ( P = 0.028). In addition, the two-way interaction of HOTTIP rs17501292- MALAT1 rs619586 polymorphisms showed a decreased effect on HCC risk ( P interaction = 0.028, OR = 0.30) and epistasis with each other. HOTTIP rs3807598 variant genotype showed significantly longer survival time in HBV negative subgroup ( P = 0.049, HR = 0.12), and MALAT1 rs591291 showed significantly better prognosis in female and HBV negative subgroups ( P = 0.022, HR = 0.37; P = 0.042, HR = 0.25, respectively). In the study, no significant effect was observed in eQTL analysis., Conclusion: Specific lncRNA ( HOTTIP and MALAT1 ) SNPs have potential to be biomarkers for HCC risk and prognosis., Competing Interests: Conflict-of-interest statement: All authors disclose no conflicts of interest that may bias their work.

Background: How germline single nucleotide polymorphisms are involved in the etiology of medulloblastoma remans poorly understood. We hypothesized that CCDKN2A/B rs1063192 and rs4977756 and also the long noncoding RNA (lncRNA) CDKN2BAS rs2157719 glioma susceptibility polymorphisms identified by genome-wide association studies may contribute to medulloblastoma predisposition., Methods: To test this hypothesis, we genotyped these genetic variants among 160 medulloblastoma patients and 443 health controls in a Chinese population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression., Results: We found that only the lncRNA CDKN2BAS rs2157719 T>C genetic polymorphism was significantly associated with an increased medulloblastoma risk (C allele: OR = 1.85, 95% CI = 1.32-2.58; p = 2.7 × 10 -4 ). The stratified analyses showed an elevated risk of pediatric medulloblastoma associated with CDKN2BAS rs2157719 CC or TC genotype (both p < 0.05). Moreover, the association between the CDKN2BAS rs2157719 polymorphism and medulloblastoma risk is more pronounced in males (OR = 2.22, 95% CI = 1.36-3.62; p = 0.001)., Conclusions: The findings of the present study provide important insights into the genetic complexities and predisposition of medulloblastoma in Chinese, especially at the lncRNA germline variation level., (Copyright © 2017 John Wiley & Sons, Ltd.)

Whether long non-coding RNA (lncRNA) single-nucleotide polymorphisms (SNPs) affect prognosis of acute myeloid leukemia (AML) remains unknown. To search the association between lncRNA SNPs and AML outcomes, thirty tagSNPs in five lncRNAs were genotyped in 313 AML patients. Survival analysis indicated that GAS5 rs55829688 (T > C) was significantly associated with prognosis of AML (p = 0.018). Patients with rs55829688 CC genotype showed higher GAS5 expression in peripheral blood mononuclear cells (PBMCs) (p = 0.025) and harbored a longer platelets recovery (p = 0.040) than carriers of rs55829688T allele. In vitro study indicated that GAS5 promoter harboring the rs55829688C allele showed marginally increased reporter gene activity (p = 0.019), and the promoter activity was increased by TP63 in a dose-dependent manner (P = 0.001). Moreover, GAS5 higher expression predict shorter AML overall survival (OS), which validated in GEO GSE12417 dataset (p = 0.011). In conclusion, rs55829688 polymorphism could increase GAS5 expression by interacting with TP63, which might aggravate the myelosuppression and in turn lead to poor prognosis in AML. Trail registration number: ChiCTR-PPC-14005297.

Esophageal squamous cell carcinoma (ESCC) may be caused by a combination of environmental factors and genetic variants. The present study was to evaluate the association between haplotype-tagging SNPs (htSNPs) of lincRNA-NR&#95;024015 and the risk of ESCC. We selected htSNPs across the whole 1469 bp lincRNA-NR&#95;024015 locus and 2 kb upstream as well as 2 kb downstream regions of the gene and conducted a case-control study in 581 ESCC cases and 677 healthy controls to test the effects of functional lincRNA-NR&#95;024015 htSNPs on ESCC susceptibility. Of the seven potential functional htSNPs, rs8506 AA genotype was found to be associated with increased risk of ESCC. Further stratification analysis showed that the risk effect was more pronounced in male patients and patients with TNM stage III and IV. LincRNA-NR&#95;024015 was predominantly expressed in cytoplasm of esophageal cancer cells. The expression level of lincRNA-NR&#95;024015 in ESCC tumor tissues was significantly higher than that in corresponding normal tissues and rs8506 genotype has a genotype-specific effect on lincRNA-NR&#95;024015 expression. Furthermore, rs8506 G to A variant might influence lincRNA-NR&#95;024015 expression and function by disrupting the binding of hsa-miR-526b to the site. High expression level of lincRNA-NR&#95;024015 and rs8506 A allele were associated with poor ESCC patients' survival. These findings indicate that functional polymorphism rs8506 G>A in lincRNA-NR&#95;024015 exon may be a genetic modifier for the development of ESCC and lincRNA-NR&#95;024015 may be a useful marker for the prediction of the biological behavior of ESCC. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Gastric cancer (GC) is a consequence of multifactorial and multistep processes. Helicobacter pylori (H. pylori) infection plays a crucial role in gastric carcinogenesis. Long non-coding RNAs (lncRNAs) have shown great potential as powerful cancer biomarkers. To investigate the possible roles of lncRNAs and H. pylori infection in GC development, we measured expression levels of three lncRNAs (H19, LINC00152, uc001lsz) in serum from a total of 285 Chinese participants using reverse transcription-quantitative polymerase chain reaction. We found significant associations between high expression of both H19 and LINC00152 in serum and increased risk of GC; the adjusted OR for H19 was 2.17 (95% CI: 1.21-3.88), and for LINC00152 was 2.09 (95% CI: 1.18-3.70). Further analyses indicated an elevated risk of GC in subjects with both high H19 expression and H. pylori infection (OR: 13.75, 95% CI: 4.75-39.84). Significant joint effect between LINC00152 and H. pylori infection on risk of GC was also found (OR: 17.49, 95% CI: 4.78-63.92). Serum H19 and LINC00152 may serve as potential biomarkers for diagnosis of GC, particularly for those with H. pylori infection., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

H19 is an imprinted gene transcribing a long non-coding RNA and is downregulated postnatally. Re-expression of H19 has been observed in patients with atherosclerosis. However, to date, no data has been published on the association of H19 polymorphisms with the risk of coronary artery disease (CAD). In this study, four polymorphisms, rs217727, rs2067051, rs2251375, rs4929984, were analyzed in 701 CAD patients and 873 age- and sex-matched control subjects. Polymorphisms were genotyped by TaqMan technology. Our data showed that the T variant of rs217727 was associated with an increased risk of CAD [additive model: odds ratio (OR)=2.05, 95%CI=1.35-3.12; dominant model: OR=1.46, 95% confidence interval (CI)=1.12-1.90; recessive model: OR=1.75, 95%CI=1.18-2.58], while A variant of rs2067051 was associated with a decreased risk of CAD (additive model: OR=0.66, 95%CI=0.45-0.96; recessive model: OR=0.71, 95%CI=0.50-0.99). Combined analysis showed that subjects carrying 3 or 4 risk alleles had a significantly increased risk of CAD, relative to those with 0-2 risk alleles (OR=1.61, 95%CI=1.20-2.15). Moreover, CAD patients with 3 or 4 risk alleles also had significantly higher Gensini scores than those with 0-2 risk alleles (P=0.001). Further haplotype-based analysis revealed that individuals with C-G-C-C, T-G-A-A, and T-A-A-A haplotypes indicated a higher prevalence of CAD (OR=1.88, 95%CI=1.03-3.43; OR=2.26, 95%CI=1.19-4.31; OR=2.66, 95%CI=1.34-5.25, respectively), compared to individuals with the most common C-G-A-C haplotype. In conclusion, our study demonstrates for the first time that common polymorphisms of H19 are associated with the risk and severity of CAD in a Chinese population. Future studies are needed to explore the underlying mechanisms of our findings., (Copyright © 2014 Elsevier B.V. All rights reserved.)