LncRNA ACTA2-AS1 Inhibits Tumorigenesis of Prostate Cancer by Maintaining ACTA2 Expression.

Abstract

The antisense transcripts play key roles in the pathogenesis of cancer. Long noncoding RNA (lncRNA) ACTA2 antisense RNA 1 (ACTA2-AS1) has been reported to inhibit the development of several cancers. In this article, the roles of ACTA2-AS1 and ACTA2 in prostate cancer (PCa) were investigated. The ACTA2-AS1 and ACTA2 expression levels in PCa samples were evaluated using GEPIA database. RT-qPCR or western blotting was used to measure their expression in PCa cells. The effects of ACTA2-AS1 and ACTA2 on PCa cell proliferation, cell cycle, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis were detected using colony formation, wound healing, transwell, flow cytometry, and western blotting. Xenograft tumor models were used to evaluate the effects of ACTA2-AS1 and ACTA2 on tumor growth. Subcellular localization, luciferase report, and RNA stability assay were performed to detect how ACTA2-AS1 modulates ACTA2 expression in PCa. We found that ACTA2-AS1 and ACTA2 were downregulated in PCa and there was a positive relationship between ACTA2-AS1 expression and ACTA2 expression in PCa samples. Overexpression of ACTA2-AS1 inhibited cell proliferation, cell cycle, migration, invasion, EMT, and promoted apoptosis, while knockdown of ACTA2-AS1 exerted opposite results. Silencing ACTA2 reversed the antitumor effect of ACTA2-AS1 overexpression on PCa in vitro and in vivo. Mechanistically, ACTA2-AS1 positively modulated ACTA2 expression by enhancing ACTA2 promoter activity to stabilize ACTA2 mRNA. Overall, ACTA2-AS1 inhibits PCa cell growth, migration, invasion, EMT, tumor growth and promotes apoptosis by enhancing ACTA2 mRNA stability, suggesting that ACTA2-AS1 may be an effective therapeutic target for PCa.