J Cancer 2020; 11(6):1614-1624. doi:10.7150/jca.41888
MiR-142-3p functions as an oncogene in prostate cancer by targeting FOXO1
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
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
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