miR-203 inhibits cell proliferation and ERK pathway in prostate cancer by targeting IRS-1

Abstract

Abstract Introduction Prostate cancer (PCa) is one of the most common types of cancer in men. In the course of the development and progression of this disease, abnormal expression of miR-203 is usually accompanied. However, its role in prostate tumorigenesis and the underlying mechanism are poorly understood. Methods Dual luciferase reporter gene analysis was used to detect miR-203 binding site in insulin receptor substrates 1 (IRS-1). Cell proliferation was assessed by MTT assay in PCa cells with either IRS-1 knockdown or miR-203 overexpression. IRS-1 and other proteins expression in PCa cells was assessed by Western Blot. Results we found that the insulin receptor substrates 1 (IRS-1) is a novel target of miR-203 in PCa and miR-203 can specifically bind to the 3′UTR region of the IRS-1 thus suppresses its expression. Moreover, we demonstrate that miR-203 functions as a tumor suppressor by directly targeting IRS-1 to inhibit cell proliferation and migration which results in PCa cell cycle arrest. Importantly, miR-203 overexpression blocks ERK signalling pathway by down-regulating IRS-1 expression. Conclusions Our results show a novel link between miR-203 and IRS-1, and reveal the importance of strict control of IRS − 1 by miR-203 in the progression of PCa, suggesting miR-203 may act as a promising target for the diagnosis and treatment of advanced PCa.

Keywords

• Prostate cancer
• miRNA
• Insulin receptor substrates 1 (IRS-1)
• Cell proliferation
• ERK pathway