LINC01535 promotes hepatocellular carcinoma proliferation and metastasis by regulating the miR-214-3p/VASP axis

TL;DR

This study shows that the lncRNA LINC01535 promotes liver cancer growth and spread by interacting with miR-214-3p and VASP, offering a new potential treatment target.

Contribution

The study identifies LINC01535 as a novel regulator of hepatocellular carcinoma progression via the miR-214-3p/VASP axis and the PI3K/AKT pathway.

Findings

LINC01535 is overexpressed in HCC tissues and cell lines.

LINC01535 promotes HCC cell proliferation, migration, and invasion by sponging miR-214-3p and upregulating VASP.

VASP activates the PI3K/AKT pathway and induces epithelial-to-mesenchymal transition in HCC.

Abstract

Background: Emerging evidence has indicated that long noncoding RNAs (lncRNAs) are associated with the development and progression of several carcinomas, including hepatocellular carcinoma (HCC). However, the role of LINC01535 in HCC is still unknown.

Materials and methods: In this study, RNA-seq, CCK-8, colony formation, wound healing, Transwell and tumor xenograft assays were used to explore the function of LINC01535 in the proliferation and metastasis of HCC in vitro and in vivo. Fluorescence in situ hybridization (FISH) assay, bioinformatics analysis, dual-luciferase assay, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis were used to reveal the interactions of LINC01535, miR-214-3p and VASP.

Results: LINC01535 was overexpressed in HCC tissues and HCC cell lines. Gain- and loss-of-function studies revealed that LINC01535 could promote HCC cell proliferation, migration and invasion both in vitro and in vivo. In addition, upregulation of LINC01535 significantly decreased the expression of microRNA-214-3p (miR-214-3p), which was found closely associated with suppressing tumor progression. Moreover, VASP was identified as a direct downstream target gene of miR-214-3p. LINC01535 positively regulated VASP expression by sponging miR-214-3p, and VASP overexpression activated the PI3K/AKT signaling pathway and stimulated epithelial-to-mesenchymal transition (EMT) in HCC.

Conclusions: Our study first found that LINC01535 promoted HCC progression by regulating its downstream target, the miR-214-3p/VASP axis, via the PI3K/AKT signaling pathway. The function and novel regulatory mechanism of LINC01535 may provide a valuable target for the diagnosis and treatment of HCC patients.

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