J Cancer 2020; 11(6):1614-1624. doi:10.7150/jca.41888

Research Paper

MiR-142-3p functions as an oncogene in prostate cancer by targeting FOXO1

Yi-Fan Tan, Zhi-Yuan Chen, Lei Wang, Min Wang, Xiu-Heng Liu

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

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Citation:
Tan YF, Chen ZY, Wang L, Wang M, Liu XH. MiR-142-3p functions as an oncogene in prostate cancer by targeting FOXO1. J Cancer 2020; 11(6):1614-1624. doi:10.7150/jca.41888. Available from https://www.jcancer.org/v11p1614.htm

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Abstract

Prostate cancer (PCa) is a heterogeneous malignancy, and is a primary cause of cancer-related death in males. Forkhead box transcription factor O1 (FOXO1) exerts antitumor effects in various cancers, including PCa. However, the regulatory mechanism of miR-142-3p on FOXO1 expression in human PCa has not been characterized. In this study, we showed that FOXO1 protein levels were downregulated in PCa tissues and cells. Moreover, FOXO1 expression was a predictor of disease-free survival in patients with PCa and was a predictor of prognosis. Increased expression of FOXO1 suppressed cellular proliferation and induced cell cycle arrest at G0/G1 in vitro. However, FOXO1 mRNA and protein levels were inconsistent in human PCa tissues and cell lines. We showed that miR-142-3p levels were negatively correlated with FOXO1 protein levels in PCa. We also showed that miR-142-3p suppressed FOXO1 expression by directly targeting its 3′-untranslated region. Furthermore, suppression of miR-142-3p inhibited cell proliferation and induced cell cycle arrest, and these effects were blocked by FOXO1 knockdown. In vivo experiments showed that miR-142-3p knockout impaired tumor growth. Our results validate that FOXO1 acted as a tumor suppressor in PCa and demonstrated that FOXO1 was regulated by miR-142-3p, and miR-142-3p may be a potential target for treatment of PCa.

Keywords: Prostate cancer, MicroRNA, MiR-142-3p, FOXO1