Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells

• Published in: Biochemical and biophysical research communications 2018-05, Vol.499 (3), p.702-710
• Main Authors: Chen, Hui, Yang, Fan, Li, Xun, Gong, Zuo-Jiong, Wang, Lu-Wen
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Apoptosis - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Cycle - genetics; Cell Line, Tumor; CELL PROLIFERATION; death; disease course; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic; hepatoma; HEPATOMAS; Humans; Inhibitor of Apoptosis Proteins - metabolism; Invasion; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; LNC473; loss-of-function mutation; Male; Middle Aged; neoplasm cells; Neoplasm Invasiveness; non-coding RNA; oncogene proteins; ONCOGENES; pro-apoptotic proteins; prognosis; Proliferation; Protein Stability; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Survivin; therapeutics; tissues; Ubiquitin Thiolesterase - metabolism; Ubiquitination; Up-Regulation - genetics; USP9X
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.03.215

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Recent studies reported that lncRNA LINC00473 (LNC473) was involved in cancer progression. However, the clinical significance and functional role of LNC473 in HCC progression is still unknown. In the present study, we found that the LNC473 expression was markedly elevated in HCC tissues and correlated with bigger tumor size, higher BCLC stage, vascular invasion and poor prognosis. Gain- and loss-of-function assay showed that LNC473 enhanced HCC cell proliferation and invasion and induced epithelial–mesenchymal transition (EMT) process. Mechanistically, LNC473 associated with oncoprotein survivin and regulates its stability. Moreover, LNC473 could recruit deubiquitinase USP9X to inhibit the ubiquitination level of survivin and then increase survivin expression. Therefore, our results suggest that LNC473 exerts its functions as an oncogene in HCC progression and may be a therapeutic target for HCC treatment. •LNC473 was overexpressed in HCC tissues and correlated with tumor size, BCLC stage, vascular invasion and poor prognosis.•LNC473 enhanced HCC cell proliferation and invasion and induced epithelial–mesenchymal transition (EMT) process.•LNC473 associated with oncoprotein survivin and regulates its stability.•LNC473 recruited USP9X to inhibit survivin ubiquitination and then increase its expression.