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10. METTL3‐stabilized super enhancers‐lncRNA SUCLG2‐AS1 mediates the formation of a long‐range chromatin loop between enhancers and promoters of SOX2 in metastasis and radiosensitivity of nasopharyngeal carcinoma

Author

Hu, Xinyu, primary, Wu, Jianfeng, additional, Feng, Yong, additional, Ma, Hongxia, additional, Zhang, Erbao, additional, Zhang, Chang, additional, Sun, Qi, additional, Wang, Tingting, additional, Ge, Yizhi, additional, Zong, Dan, additional, Chen, Wei, additional, and He, Xia, additional

Published
2023
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15. Additional file 1 of B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma

Author

Cui, Yanan, Li, Jun, Zhang, Pengpeng, Yin, Dandan, Wang, Ziyu, Dai, Jiali, Wang, Wei, Zhang, Erbao, and Guo, Renhua

Abstract

Additional file 1: Figure S1. (A-B) qRT-PCR was performed to detect the B4GALT1 mRNA expression after siRNA-mediated knockdown and plasmid-mediated overexpression in A549 and PC9 cells. (C) Western blot was performed to detect the B4GALT1 protein expression. (D) The protein expression levels of CDK4 and Cyclin D1 in control and ectopic B4GALT1-expressing A549 and PC9 cells were determined using western blotting analyses. * P < 0.05, ** P < 0.01. Figure S2. (A) The linear correlations between the B4GALT1 expression and the CD8+ T-cell expression in the TCGA-LUAD dataset. (B) Comparison of TIDE scores between the B4GALT1-high group and B4GALT1-low group. (C) Comparison of overall survival between CTL top (samples above average CTL values among all samples) and CTL bottom (samples below average CTL values among all samples) groups in patients with different B4GALT1 levels. The two-sided Wald test in the Cox-PH regression was applied to compute the association between the CTL level and overall survival, and samples were split by the best separation strategy according to the B4GALT1 expression coefficients in the Cox-PH regression model. ** P < 0.01. Figure S3. (A-B) The differential expression of CD274 in tumours with high expression of B4GALT1 and low expression of B4GALT1 in the CCLE mRNA dataset (A) and the differential expression of PD-L1 in tumours with high expression of B4GALT1 and low expression of B4GALT1 in the TCGA-protein dataset (B). RPKM: reads per kilobase per million mapped reads; RPPA: reverse phase protein array. (C) Representative immunohistochemical images (left panel) and the association between B4GALT1 and PD-L1 level in MPLC tumours (right panel). Scale bars, 200 μm. (D) qRT-PCR was performed to detect the B4galt1 mRNA expression after siRNA-mediated knockdown in LLC cells. (E-F) LLC cells were transfected with si-B4galt1 or pcDNA- B4galt1, and Cd274 mRNA and PD-L1 protein was analysed by qRT-PCR and western blotting analyses. (G) LLC cells cocultured with activated CD8+ T cells for 48 h were subjected to crystal violet staining and quantified at 570 nm. The ratio of LLC cells to T cells is 1:3. (H) Western blot analysis of PD-L1 expression in LLC cells with or without the knockdown or overexpression of B4galt1 followed by the treatment with CHX. (I) Western blot analysis of PD-L1 levels in B4galt1 knock-down cells, B4galt1 overexpression cells, and tunicamycin (TM) treated cells. * P < 0.05, ** P < 0.01, ****P

Published
2023
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20. Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinoma

Author

Zhang, Chang, primary, Sun, Qi, additional, Zhang, Xu, additional, Qin, Na, additional, Pu, Zhening, additional, Gu, Yayun, additional, Yan, Caiwang, additional, Zhu, Meng, additional, Dai, Juncheng, additional, Wang, Cheng, additional, Li, Ni, additional, Jin, Guangfu, additional, Ma, Hongxia, additional, Hu, Zhibin, additional, Zhang, Erbao, additional, Tan, Fengwei, additional, and Shen, Hongbing, additional

Published
2022
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21. Additional file 2 of Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake in lung adenocarcinoma

Author

Liu, Tongyan, Han, Chencheng, Fang, Panqi, Ma, Zhifei, Wang, Xiaoxiao, Chen, Hao, Wang, Siwei, Meng, Fanchen, Wang, Cheng, Zhang, Erbao, Dong, Guozhang, Zhu, Hongyu, Yin, Wenda, Wang, Jie, Zuo, Xianglin, Qiu, Mantang, Wang, Jinke, Qian, Xu, Shen, Hongbing, Xu, Lin, Hu, Zhibin, and Yin, Rong

Abstract

Additional file 2. Supplementary Figures.

Published
2022
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25. A cross-tissue transcriptome-wide association study identifies novel susceptibility genes for lung cancer in Chinese populations

Author

Zhu, Meng, primary, Fan, Jingyi, additional, Zhang, Chang, additional, Xu, Jing, additional, Yin, Rong, additional, Zhang, Erbao, additional, Wang, Yuzhuo, additional, Ji, Mengmeng, additional, Sun, Qi, additional, Dai, Juncheng, additional, Jin, Guangfu, additional, Chen, Liang, additional, Xu, Lin, additional, Hu, Zhibin, additional, Ma, Hongxia, additional, and Shen, Hongbing, additional

Published
2021
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26. Genetic variants associated with expression of TCF19 contribute to the risk of head and neck cancer in Chinese population

Author

Ji, Pei, primary, Chang, Jiang, additional, Wei, Xiaoyu, additional, Song, Xueyao, additional, Yuan, Hua, additional, Gong, Linnan, additional, Li, Yuancheng, additional, Ding, Dongsheng, additional, Zhang, Erbao, additional, Yan, Caiwang, additional, Zhu, Meng, additional, Miao, Xiaoping, additional, Wu, Chen, additional, Jin, Guangfu, additional, Hu, Zhibin, additional, Shen, Hongbing, additional, and Ma, Hongxia, additional

Published
2021
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27. A novel long non-coding RNA NFIA-AS1 is down-regulated in gastric cancer and inhibits proliferation of gastric cancer cells

Author

Lu Xiyi, He Xuezhi, Wang Jing, Amin Karim Muhammad, Miao Dengshun, and Zhang Erbao

Subjects
Tumor suppressor gene, business.industry, Cancer, General Medicine, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Long non-coding RNA, Antisense RNA, Real-time polymerase chain reaction, NFIA, Cancer cell, Cancer research, Medicine, Biomarker (medicine), Original Article, business
Abstract

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.

Published
2019

28. Comprehensive characterization of functional eRNAs in lung adenocarcinoma reveals novel regulators and a prognosis-related molecular subtype

Author

Qin, Na, primary, Ma, Zijian, additional, Wang, Cheng, additional, Zhang, Erbao, additional, Li, Yuancheng, additional, Huang, Mingtao, additional, Chen, Congcong, additional, Zhang, Chang, additional, Fan, Jingyi, additional, Gu, Yayun, additional, Xu, Xianfeng, additional, Yang, Liu, additional, Wei, Xiaoxia, additional, Yin, Rong, additional, Jiang, Yue, additional, Dai, Juncheng, additional, Jin, Guangfu, additional, Xu, Lin, additional, Hu, Zhibin, additional, Shen, Hongbing, additional, and Ma, Hongxia, additional

Published
2020
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30. Genetic variants associated with expression of TCF19contribute to the risk of head and neck cancer in Chinese population

Author

Ji, Pei, Chang, Jiang, Wei, Xiaoyu, Song, Xueyao, Yuan, Hua, Gong, Linnan, Li, Yuancheng, Ding, Dongsheng, Zhang, Erbao, Yan, Caiwang, Zhu, Meng, Miao, Xiaoping, Wu, Chen, Jin, Guangfu, Hu, Zhibin, Shen, Hongbing, and Ma, Hongxia

Abstract

BackgroundSquamous cell carcinoma of the head and neck (SCCHN) is one of the most common cancers worldwide and includes cancers arising from the oral cavity, pharynx and larynx. Genome-wide association studies have found several genetic variants related to the risk of SCCHN; however, they could only explain a small fraction of the heritability. Thus, more susceptibility loci associated with SCCHN need to be identified.MethodsAn association study was conducted by genotyping 555 patients with SCCHN and 1367 controls in a Chinese population. Single-variant association analysis was conducted on 63 373 SNPs, and the promising variants were then confirmed by a two-stage validation with 1875 SCCHN cases and 4637 controls. Bioinformatics analysis and functional assays were applied to uncover the potential pathogenic mechanism of the promising variants and genes associated with SCCHN.ResultsWe first identified three novel genetic variants significantly associated with the risk of SCCHN (p=7.45×10−7for rs2517611 at 6p22.1, p=1.76×10−9for rs2524182 at 6p21.33 and p=2.17×10−10for rs3131018 at 6p21.33). Further analysis and biochemical assays showed that rs3094187, which was in a region in high linkage disequilibrium with rs3131018, could modify TCF19expression by regulating the binding affinity of the transcription factor SREBF1to the promoter of TCF19. In addition, experiments revealed that the inhibition of TCF19may affect several important pathways involved in tumourigenesis and attenuate the cell proliferation and migration of SCCHN.ConclusionThese findings offer important evidence that functional genetic variants could contribute to development of SCCHN and that TCF19may function as a putative susceptibility gene for SCCHN.

Published
2022
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31. A cis‐eQTL genetic variant in PLK4 confers high risk of hepatocellular carcinoma

Author

Meng, Lijuan, primary, Zhou, Yan, additional, Ju, Sihan, additional, Han, Jing, additional, Song, Ci, additional, Kong, Jing, additional, Wu, Yifei, additional, Lu, Shuai, additional, Xu, Jiani, additional, Yuan, Wenwen, additional, Zhang, Erbao, additional, Wang, Cheng, additional, Hu, Zhibin, additional, Gu, Yayun, additional, Luo, Rongcheng, additional, and Wang, Xuehao, additional

Published
2019
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32. Hypomethylation‐activated cancer‐testis gene SPANXC promotes cell metastasis in lung adenocarcinoma

Author

Wang, Xuewei, primary, Ju, Sihan, additional, Chen, Yao, additional, Qian, Qufei, additional, Yan, Caiwang, additional, Chen, Shuaizhou, additional, Chang, Yuting, additional, Xu, Yide, additional, Ma, Zijian, additional, Zhang, Chang, additional, Qin, Na, additional, Gu, Yayun, additional, Wang, Cheng, additional, Zhang, Erbao, additional, and Hu, Zhibin, additional

Published
2019
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33. Comprehensive characterization of cancer‐testis genes in testicular germ cell tumor

Author

Chang, Yuting, primary, Wang, Xuewei, additional, Xu, Yide, additional, Yang, Liu, additional, Qian, Qufei, additional, Ju, Sihan, additional, Chen, Yao, additional, Chen, Shuaizhou, additional, Qin, Na, additional, Ma, Zijian, additional, Dai, Juncheng, additional, Ma, Hongxia, additional, Jin, Guangfu, additional, Zhang, Erbao, additional, Wang, Cheng, additional, and Hu, Zhibin, additional

Published
2019
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34. Gene amplification derived a cancer‐testis long noncoding RNA PCAT6 regulates cell proliferation and migration in hepatocellular carcinoma

Author

Chen, Shuaizhou, primary, Chen, Yao, additional, Qian, Qufei, additional, Wang, Xuewei, additional, Chang, Yuting, additional, Ju, Sihan, additional, Xu, Yide, additional, Zhang, Chang, additional, Qin, Na, additional, Ding, Hui, additional, Gu, Yayun, additional, Han, Jing, additional, Wang, Cheng, additional, Zhang, Erbao, additional, and Hu, Zhibin, additional

Published
2019
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36. A cancer-testis non-coding RNA LIN28B-AS1 activates driver gene LIN28B by interacting with IGF2BP1 in lung adenocarcinoma

Author

Wang, Cheng, primary, Gu, Yayun, additional, Zhang, Erbao, additional, Zhang, Kai, additional, Qin, Na, additional, Dai, Juncheng, additional, Zhu, Meng, additional, Liu, Jia, additional, Xie, Kaipeng, additional, Jiang, Yue, additional, Guo, Xuejiang, additional, Liu, Mingxi, additional, Jin, Guangfu, additional, Ma, Hongxia, additional, Jiang, Tao, additional, Yin, Rong, additional, Xia, Yankai, additional, Liu, Li, additional, Wang, Shouyu, additional, Shen, Bin, additional, Huo, Ran, additional, Xu, Lin, additional, Sha, Jiahao, additional, Qu, Bin, additional, Shen, Hongbing, additional, and Hu, Zhibin, additional

Published
2018
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37. Long noncoding RNA cytoskeleton regulator RNA promotes cell invasion and metastasis by titrating miR‐613 to regulate ANXA2 in nasopharyngeal carcinoma.

Author

Chen, Wei, Du, Mingyu, Hu, Xinyu, Ma, Hongxia, Zhang, Erbao, Wang, Tingting, Yin, Li, He, Xia, and Hu, Zhibin

Subjects
NON-coding RNA, CELL migration, WESTERN immunoblotting, RNA, METASTASIS
Abstract

Background: Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors. Long noncoding RNAs play critical roles in tumorigenesis. Methods: Real‐time quantitative PCR arrays were used to evaluate the expression levels of cytoskeleton regulator RNA (CYTOR) in NPC tissues and cells. Cell counting kit‐8 and colony formation analyses were used to test the NPC cell viability, while wound healing and transwell assays were employed to detect cell invasion and migration ability. Luciferase reporter assay and Western blot analyses were employed to explore the relationships among CYTOR, miR‐613, and ANXA2. Results: We found that CYTOR expression was elevated both in NPC tissues and cells. Functional assays revealed that CYTOR promoted the invasion and migration of NPC cells. The established spontaneous lymph node metastasis model also confirmed that CYTOR promoted NPC cell metastasis in vivo. Mechanically, we found that the subcellular localization of CYTOR mostly occurred in the cell cytoplasm. Luciferase reporter and RIP assays confirmed that CYTOR functioned as the molecular sponge of miR‐613. Subsequent experiments confirmed that ANXA2 was directly targeted by miR‐613. Gain‐ and loss‐of‐function studies further confirmed that CYTOR induced the upregulation of ANXA2 by competitively binding to miR‐613, thus leading to NPC metastasis. Conclusion: Our results highlight the importance of CYTOR in NPC development and provide new insights into potential therapeutic targets for NPC. [ABSTRACT FROM AUTHOR]

Published
2020
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39. The Circular RNA circPRKCI Promotes Tumor Growth in Lung Adenocarcinoma

Author

Qiu, Mantang, primary, Xia, Wenjia, additional, Chen, Rui, additional, Wang, Siwei, additional, Xu, Youtao, additional, Ma, Zhifei, additional, Xu, Weizhang, additional, Zhang, Erbao, additional, Wang, Jie, additional, Fang, Tian, additional, Hu, Jingwen, additional, Dong, Gaochao, additional, Yin, Rong, additional, Wang, Jun, additional, and Xu, Lin, additional

Published
2018
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42. H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma

Author

Zhang, Erbao, primary, Han, Liang, additional, Yin, Dandan, additional, He, Xuezhi, additional, Hong, Linzhi, additional, Si, Xinxin, additional, Qiu, Mantang, additional, Xu, Tongpeng, additional, De, Wei, additional, Xu, Lin, additional, Shu, Yongqian, additional, and Chen, Jinfei, additional

Published
2016
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43. LncRNA H19 confers chemoresistance in ERα-positive breast cancer through epigenetic silencing of the pro-apoptotic gene BIK

Author

Si, Xinxin, primary, Zang, Ruochen, additional, Zhang, Erbao, additional, Liu, Yue, additional, Shi, Xiao, additional, Zhang, Ershao, additional, Shao, Lipei, additional, Li, Andi, additional, Yang, Nan, additional, Han, Xiao, additional, Pan, Beijing, additional, Zhang, Zhihong, additional, Sun, Luan, additional, and Sun, Yujie, additional

Published
2016
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44. E2F1-induced upregulation of long noncoding RNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs

Author

Zhang, Erbao, primary, Yin, Dandan, additional, Han, Liang, additional, He, Xuezhi, additional, Si, Xinxin, additional, Chen, Wenming, additional, Xia, Rui, additional, Xu, Tongpeng, additional, Gu, Dongying, additional, De, Wei, additional, Guo, Renhua, additional, Xu, Zhi, additional, and Chen, Jinfei, additional

Published
2015
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45. A cancer-testis non-coding RNA LIN28B-AS1activates driver gene LIN28Bby interacting with IGF2BP1 in lung adenocarcinoma

Author

Wang, Cheng, Gu, Yayun, Zhang, Erbao, Zhang, Kai, Qin, Na, Dai, Juncheng, Zhu, Meng, Liu, Jia, Xie, Kaipeng, Jiang, Yue, Guo, Xuejiang, Liu, Mingxi, Jin, Guangfu, Ma, Hongxia, Jiang, Tao, Yin, Rong, Xia, Yankai, Liu, Li, Wang, Shouyu, Shen, Bin, Huo, Ran, Xu, Lin, Sha, Jiahao, Qu, Bin, Shen, Hongbing, and Hu, Zhibin

Abstract

Our previous work found cancer-testis (CT) genes as a new source of epi-driver candidates of cancer. LIN28Bwas a CT gene, but the “driver” ability and the activation mechanism in lung adenocarcinoma (LUAD) remain unclear. We observed that LIN28Bexpression was restricted in testis. It was re-activated in LUAD patients without known genomic alterations in oncogenes and was related to poorer survival. In vitro and In vivo experiments confirmed that the activation of LIN28Bcould promote the proliferation and metastasis of LUAD cells and can influence cell cycle, DNA damage repair, and genome instability. In addition to the known let-7-LIN28B regulation loop, our results further revealed a let-7-independent Cis-regulator of LIN28B: LIN28B-AS1. LIN28B-AS1is a CT long non-coding RNA (CT-lncRNA). It altered the messenger RNA stability of LIN28Bby directly interacting with another CT protein IGF2BP1 but not with LIN28B and constituted a novel regulation network. In sum, we identify that LIN28Bis an “epi-driver” of LUAD and clarify a new lncRNA-activated mechanism of LIN28B, which provide new candidate targets for precise anticancer therapy in the future.

Published
2019
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46. Genetic variants associated with expression of TCF19 contribute to the risk of head and neck cancer in Chinese population.

Author

Ji P, Chang J, Wei X, Song X, Yuan H, Gong L, Li Y, Ding D, Zhang E, Yan C, Zhu M, Miao X, Wu C, Jin G, Hu Z, Shen H, and Ma H

Subjects
Case-Control Studies, China epidemiology, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide genetics, Squamous Cell Carcinoma of Head and Neck genetics, Transcription Factors genetics, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Head and Neck Neoplasms epidemiology, Head and Neck Neoplasms genetics
Abstract

Background: Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common cancers worldwide and includes cancers arising from the oral cavity, pharynx and larynx. Genome-wide association studies have found several genetic variants related to the risk of SCCHN; however, they could only explain a small fraction of the heritability. Thus, more susceptibility loci associated with SCCHN need to be identified., Methods: An association study was conducted by genotyping 555 patients with SCCHN and 1367 controls in a Chinese population. Single-variant association analysis was conducted on 63 373 SNPs, and the promising variants were then confirmed by a two-stage validation with 1875 SCCHN cases and 4637 controls. Bioinformatics analysis and functional assays were applied to uncover the potential pathogenic mechanism of the promising variants and genes associated with SCCHN., Results: We first identified three novel genetic variants significantly associated with the risk of SCCHN (p=7.45×10 -7 for rs2517611 at 6p22.1, p=1.76×10 -9 for rs2524182 at 6p21.33 and p=2.17×10 -10 for rs3131018 at 6p21.33). Further analysis and biochemical assays showed that rs3094187, which was in a region in high linkage disequilibrium with rs3131018, could modify TCF19 expression by regulating the binding affinity of the transcription factor SREBF1 to the promoter of TCF19 . In addition, experiments revealed that the inhibition of TCF19 may affect several important pathways involved in tumourigenesis and attenuate the cell proliferation and migration of SCCHN., Conclusion: These findings offer important evidence that functional genetic variants could contribute to development of SCCHN and that TCF19 may function as a putative susceptibility gene for SCCHN., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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47. EZH2-Mediated Epigenetic Suppression of GDF15 Predicts a Poor Prognosis and Regulates Cell Proliferation in Non-Small-Cell Lung Cancer.

Author

Lu X, He X, Su J, Wang J, Liu X, Xu K, De W, Zhang E, Guo R, and Shi YE

Abstract

Growth differentiation factor 15 (GDF15), a member of the TGF-β superfamily of cytokines, has been reported to exert very heterogeneous functions in various tumors. However, its expression and roles in mediating non-small-cell lung cancer (NSCLC) progression remain unknown. In this study, we found that GDF15 is downregulated in paired NSCLC tissues and correlated with poor clinical outcomes in NSCLC. A functional experiment demonstrated that overexpression of GDF15 significantly repressed NSCLC proliferation both in vitro and in vivo. Mechanistic studies reveal that inhibition of EZH2 expression prevented its binding to the GDF15 promoter region and reduced the trimethylation modification pattern of H3K27. Together, our data uncover that GDF15 is a direct target of EZH2 and, as a regulator of proliferation, might serve as a candidate prognostic biomarker and target for new therapies in human NSCLC., (Copyright © 2018. Published by Elsevier Inc.)

Published
2018
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48. H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma.

Author

Zhang E, Han L, Yin D, He X, Hong L, Si X, Qiu M, Xu T, De W, Xu L, Shu Y, and Chen J

Subjects
Acetylation, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Cell Movement, Cell Proliferation, Enhancer of Zeste Homolog 2 Protein metabolism, Esophageal Neoplasms metabolism, Esophageal Neoplasms pathology, Esophageal Squamous Cell Carcinoma, Female, Gene Silencing, Homeodomain Proteins metabolism, Humans, Intracellular Signaling Peptides and Proteins metabolism, Male, Methyltransferases metabolism, MicroRNAs metabolism, Middle Aged, Nerve Tissue Proteins metabolism, Prognosis, RNA, Long Noncoding physiology, Repressor Proteins metabolism, Carcinoma, Squamous Cell genetics, Esophageal Neoplasms genetics, Gene Expression Regulation, Neoplastic, Histones metabolism, Homeodomain Proteins genetics, Intracellular Signaling Peptides and Proteins genetics, Nerve Tissue Proteins genetics, RNA, Long Noncoding metabolism
Abstract

Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. In our study, we found that lncRNA CCAT1, whose expression is significantly increased and is correlated with outcomes in Esophageal Squamous Cell Carcinoma (ESCC). Consecutive experiments confirmed that H3K27-acetylation could activate expression of colon cancer associated transcript-1 (CCAT1). Further experiments revealed that CCAT1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. RNA-seq analysis revealed that CCAT1 knockdown preferentially affected genes that are linked to cell proliferation, cell migration and cell adhesion. Mechanistic investigations found that CCAT1 could serve as a scaffold for two distinct epigenetic modification complexes (5΄ domain of CCAT1 binding Polycomb Repressive Complex 2 (PRC2) while 3΄ domain of CCAT1 binding SUV39H1) and modulate the histone methylation of promoter of SPRY4 (sprouty RTK signaling antagonist 4) in nucleus. In cytoplasm, CCAT1 regulates HOXB13 as a molecular decoy for miR-7, a microRNA that targets both CCAT1 and HOXB13, thus facilitating cell growth and migration. Together, our data demonstrated the important roles of CCAT1 in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2017
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49. E2F1-induced upregulation of long noncoding RNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs.

Author

Zhang E, Yin D, Han L, He X, Si X, Chen W, Xia R, Xu T, Gu D, De W, Guo R, Xu Z, and Chen J

Subjects
Animals, Apoptosis, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Cyclin-Dependent Kinase Inhibitor Proteins genetics, E2F1 Transcription Factor genetics, Female, Follow-Up Studies, Gene Silencing, Humans, Lymphatic Metastasis, Male, Mice, Mice, Inbred BALB C, Middle Aged, Prognosis, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, Survival Rate, Tumor Cells, Cultured, Up-Regulation, Xenograft Model Antitumor Assays, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor Proteins antagonists & inhibitors, E2F1 Transcription Factor metabolism, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, RNA, Long Noncoding genetics, Stomach Neoplasms pathology
Abstract

Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. By utilizing publicly available lncRNAs expression profiling data and integrating analyses, we screened out LINC00668, whose expression is significantly increased and correlated with outcomes in gastric cancer (GC). Further experiments revealed that LINC00668 knockdown significantly repressed proliferation, both in vitro and in vivo. Mechanistic investigations showed that LINC00668 was a direct transcriptional target of E2F transcription factor 1 (E2F1). We further demonstrated that LINC00668 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors (CKIs), including p15, p16, p21, p27 and p57, thus contributing to the regulation of the gastric cancer cell cycle. Our results suggest that E2F1-activated LINC00668, as a cell cycle regulator, enriches the mechanistic link between lncRNA and the E2F1-mediated cell cycle regulation pathway and may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer., Competing Interests: The authors have declared that no conflict of interest exists

Published
2016
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