miR-203 inhibits cell proliferation and ERK pathway in prostate cancer by targeting IRS-1
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RESEARCH ARTICLE
Open Access
miR-203 inhibits cell proliferation and ERK pathway in prostate cancer by targeting IRS-1 Yang Meng1†, Xiaoyan Hu1†, Shasha Li1†, Xinyi Zeng1, Lei Qiu1, Mingtian Wei2, Ziqing Wang2 and Junhong Han1*
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 miR203 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 downregulating 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
Introduction Prostate cancer (PCa) is the most common type of cancer for men of over 50 years old and the fifth-leading of cancer-related death in men worldwide [1]. Increasing evidence shows that the incidence of PCa is increasing in many countries. Epigenetic alterations in DNA methylation and histone modifications are associated with tumor initiation and progression, and microRNA
* Correspondence: [email protected] † Yang Meng, Xiaoyan Hu and Shasha Li contributed equally to this work. 1 Department of Abdominal Oncology and Laboratory of Epigenetics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P.R. China Full list of author information is available at the end of the article
(miRNA)-mediated gene regulation is another epigenetic modification associated with carcinogenesis [2]. miRNAs are non-coding RNAs (approximately 22 nt in length) that function in the negative regulation of gene expression. They exert regulatory effects by binding to the 3′-untranslated region (UTR) of target mRNAs leading to mRNA degradation or transcriptional silencing in a sequence specific manner [3]. miR-203, one of the miRNA family members, was first reported to regulate embryonic epidermal differentiation and the construction of the dermal protective barrier. It has recently been show
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