LncRNA meg3 suppresses hepatocellular carcinoma in vitro and vivo studies.

Abstract

Although abnormal expression of the long non-coding RNA (lncRNA) MEG3 has been reported in multiple cancer types, the role of MEG3 in the pathobiology of hepatocellular carcinoma (HCC) remains unknown. This study evaluated the expression of lncRNA MEG3 and a microRNA (miRNA-10a-5p) implicated in HCC metastasis in cancer and carcinoma adjacent tissues of HCC samples (n=30 each) via in situ hybridization and quantitative RT-PCR. The effects of overexpressing either MEG3 alone, or MEG3 in combination with miRNA-10a-5p, on the proliferation, apoptosis, cell cycle progression, migration, and invasion of HepG2 cells were evaluated using functional assays. Dual luciferase reporter assays and western blotting were employed to delineate the mechanisms of MEG3 and miRNA-10a-5p regulation of key oncogenes and tumor suppressors in HCC cells. Compared to carcinoma-adjacent regions, MEG3 expression was downregulated in cancer regions of HCC samples; by contrast, miRNA-10a-5p was overexpressed in cancer regions compared to tumor-adjacent areas. Furthermore, overexpression of MEG3 (a) decreased proliferation, migration, and invasion of HepG2 cells; (b) enhanced apoptosis and the proportion of HepG2 cells in G1 of the cell cycle; (c) increased the expression of phosphatase and tensin homolog (PTEN), Bcl2-associated X (Bax), and p53 proteins; and (d) decreased the expression of miRNA-10a-5p, AKT, p-AKT, Bcl-2, and the matrix metalloproteinases (MMPs)-2 and -9. Furthermore, miRNA-10a-5p bound the 3-untranslated region of PTEN mRNA and downregulated PTEN protein expression. Taken together, these data suggest that MEG3 regulates the PTEN/AKT/MMP-2/MMP-9 signaling axis and contributes to HCC development by targeting miRNA-10a-5p.