PGM5-AS1 impairs miR-587-mediated GDF10 inhibition and abrogates progression of prostate cancer

• Published in: Journal of translational medicine 2021-01, Vol.19 (1), p.12-12, Article 12
• Main Authors: Du, Lei, Gao, Yongli
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Antisense RNA; Apoptosis; Bone morphogenetic proteins; Care and treatment; Cell cycle; Cell Line, Tumor; Cell Proliferation; Colorectal cancer; Development and progression; Expression vectors; Fluorides; GDF10; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Growth Differentiation Factor 10; Health aspects; Humans; Immunoprecipitation; Laboratory animals; Male; Medical research; Metastasis; Mice; Mice, Nude; MicroRNA-587; MicroRNAs; MicroRNAs - genetics; miRNA; Non-coding RNA; PGM5-AS1; Physiological aspects; Plasmids; Proliferation; Prostate cancer; Prostatic Neoplasms - genetics; Proteins; Reporter gene; RNA; RNA, Long Noncoding - genetics; RNA-binding protein; Tumorigenicity; Xenografts
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02572-w

Prostate cancer (PCa) is a leading cause of cancer-related death in males. Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in various human malignancies, including PCa. This study aims to clarify the inhibitory role of human PGM5 antisense RNA 1 (PGM5-AS1) in the proliferation and apoptosis of PCa cells. The regulatory network of PGM5-AS1/microRNA-587 (miR-587)/growth and differentiation factor 10 (GDF10) axis was examined by dual-luciferase reporter gene assay, RNA-binding protein immunoprecipitation, and RNA pull down assay. We manipulated the expression of PGM5-AS1, miR-587 and GDF10 by transducing expression vectors, mimic, inhibitor, or short hairpin RNA into PCa cells, thus establishing their functions in cell proliferation and apoptosis. Additionally, we measured the tumorigenicity of PCa cells xenografted in nude mice. PGM5-AS1 is expressed at low levels in PCa cell lines. Forced overexpression of PGM5-AS1 restricted proliferation and facilitated apoptosis of PCa cells, manifesting in suppressed xenograft tumor growth in nude mice. Notably, PGM5-AS1 competitively bound to miR-587, which directly targets GDF10. We further validated that the anti-cancer role of PGM5-AS1 in PCa cells was achieved by binding to miR-587 to promote the expression of GDF10. PGM5-AS1 upregulates GDF10 gene expression by competitively binding to miR-587, thus inhibiting proliferation and accelerating apoptosis of PCa cells.