Eur Rev Med Pharmacol Sci.2019 Apr;23(8):3291-3301.doi: 10.26355/eurrev_201904_17691.

Increased long noncoding RNA LINC00511 is correlated with poor prognosis and contributes to cell proliferation and metastasis by modulating miR-424 in hepatocellular carcinoma

R-P Wang  1 J JiangT JiangY WangL-X Chen Affiliations

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Objective: Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in human hepatocellular carcinoma (HCC) and associated with the progression of HCC. LncRNA LINC00511 (LINC00511) has been confirmed to act as a tumor promoter in several tumors. However, as a novel lncRNA, the specific effect of LINC00511 is still largely obscure. In this study, we aimed to evaluate the effect of LINC00511 in HCC behaviors and to elucidate the mechanism by which this occurs.

Patients and methods: The expressions of LINC00511 in HCC tissues and cell lines were evaluated by qRT-PCR. The correlations between LINC00511 expression and the clinicopathological parameters and prognosis of HCC patients were determined using several statistical methods. CCK-8 assay, colony formation assay, flow cytometry cell cycle, apoptosis assay, EdU assay, wound healing assay, and transwell assay were used to investigate the role of LINC00511 on the malignant phenotypes in vitro. Insights into the potential mechanisms of ceRNAs were determined by bioinformatics analysis, dual-luciferase reporter assays and RT-PCR.

Results: LINC00511 expression was significantly up-regulated in HCC tissues and cell lines, and its high expression was distinctly associated with nodal metastasis, vascular invasion, and clinical stage. Furthermore, statistical assays revealed that HCC patients with higher LINC00511 expression levels had worse overall survival rates. Importantly, the multivariate analysis confirmed that LINC00511 expression was an independent prognostic factor of the overall survival in patients with HCC. Functionally, the inhibition of LINC00511 significantly suppressed the capability of proliferation, migration, and invasion in HCC cell lines. Bioinformatic tools predicted that miR-424 both targeted the 3′-UTR of LINC00511, which was confirmed using the luciferase reporter assay and RT-PCR.

Conclusions: LINC00511 plays an important role in the malignant progression of HCC via modulation of miR-424.