LncRNA SNHG6 promotes G1/S-phase transition in hepatocellular carcinoma by impairing miR-204-5p-mediated inhibition of E2F1

• Published in: Oncogene Vol. 40; no. 18; pp. 3217 - 3230
• Main Authors: Chen, Kai, Hou, Yifu, Liao, Rui, Li, Youzan, Yang, Hongji, Gong, Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-05-2021; Nature Publishing Group
• Subjects: 13/100; 631/57; 631/80; Animals; Apoptosis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Biology; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Cyclin D1; Cyclin E - genetics; Cyclin E - metabolism; Development and progression; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - metabolism; Female; G1 Phase - genetics; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Hepatocellular carcinoma; Hepatoma; Human Genetics; Humans; Internal Medicine; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Mice; Mice, Nude; MicroRNAs - genetics; Oncogene Proteins; Oncology; Phase transitions; Physiological aspects; RNA; RNA, Long Noncoding - genetics; S phase; S Phase - genetics; Transcription factors; Tumorigenesis; China
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-021-01671-2

Emerging evidence suggests that long noncoding RNAs (lncRNAs) function as competitive endogenous RNA (ceRNA) targeting proteins and genes; however, the role of lncRNAs in hepatocellular carcinoma (HCC) is not well understood. We investigated the mechanism by which lncRNA SNHG6 promotes the development of HCC. RT-qPCR revealed upregulated lncRNA SNHG6 in the HCC setting. Elevated SNHG6 expression was indicative of poor prognosis in patients with HCC. SNHG6 overexpression resulted in increased cyclin D1, cyclin E1, and E2F1 expression both in vitro and in vivo. SNHG6 also promoted HCC cell proliferation by enhancing G1-S phase transition in vitro. Dual luciferase reporter assays, RIP, and RNA pull-down assays demonstrated SNHG6 competitively bound to miR-204-5p and inhibited its expression preventing miR-204-5p from targeting E2F1. Overexpression of miR-204-5p abolished the effect of SNHG6. Our data suggest that SNHG6 functions as a ceRNA that targets miR-204-5p resulting in an increased E2F1 expression and enhanced G1-S phase transition, thereby promoting the tumorigenesis of HCC.