Long noncoding RNA FTX inhibits hepatocellular carcinoma proliferation and metastasis by binding MCM2 and miR-374a

• Published in: Oncogene Vol. 35; no. 41; pp. 5422 - 5434
• Main Authors: Liu, F, Yuan, J-H, Huang, J-F, Yang, F, Wang, T-T, Ma, J-Z, Zhang, L, Zhou, C-C, Wang, F, Yu, J, Zhou, W-P, Sun, S-H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.10.2016; Nature Publishing Group
• Subjects: 13/109; 13/31; 13/89; 14/19; 14/32; 38/1; 38/32; 38/77; 38/90; 42/44; 59/5; 631/67/1504/1610; 82/29; 82/58; 82/80; Aged; Antisense RNA; Apoptosis; Binding sites; Cancer; Cancer metastasis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell adhesion & migration; Cell Biology; Cell proliferation; Cell Proliferation - genetics; Cellular biology; Comparative analysis; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA replication; Epithelial-Mesenchymal Transition; Female; Gender; Gene Expression Regulation, Neoplastic; Hepatocellular carcinoma; Hepatology; Human Genetics; Humans; Internal Medicine; Liver; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Mesenchyme; Metastases; Metastasis; MicroRNAs - biosynthesis; MicroRNAs - genetics; Middle Aged; Minichromosome Maintenance Complex Component 2 - genetics; Neoplasm Metastasis; Oncology; original-article; Patients; Prognosis; Replication; RNA, Long Noncoding - biosynthesis; RNA, Long Noncoding - genetics; Sex Characteristics; Transcription; Tumor suppressor genes; Tumors; Wnt protein; Wnt Signaling Pathway; X-chromosome inactivation; β-Catenin
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2016.80

It has long been known that males are more susceptible than females to hepatocellular carcinoma (HCC), but the reason remains elusive. In this study, we investigated the expression and function of the long noncoding RNA FTX (lnc-FTX), an X-inactive-specific transcript (XIST) regulator transcribed from the X chromosome inactivation center, in both HCC and HCC gender disparity. lnc-FTX is expressed at higher levels in female livers than in male livers and is significantly downregulated in HCC tissues compared with normal liver tissues. Patients with higher lnc-FTX expression exhibited longer survival, suggesting that lnc-FTX is a useful prognostic factor for HCC patients. lnc-FTX inhibits HCC cell growth and metastasis both in vitro and in vivo . Mechanistically, lnc-FTX represses Wnt/β-catenin signaling activity by competitively sponging miR-374a and inhibits HCC cell epithelial–mesenchymal transition and invasion. In addition, lnc-FTX binds to the DNA replication licensing factor MCM2, thereby impeding DNA replication and inhibiting proliferation in HCC cells. In conclusion, these findings suggest that lnc-FTX may act as a tumor suppressor in HCC through physically binding miR-374a and MCM2. It may also be one of the reasons for HCC gender disparity and may potentially contribute to HCC treatment.