MicroRNA-744 promotes prostate cancer progression through aberrantly activating Wnt/?-catenin signaling.

ABSTRACT: Accumulated evidence indicate that miR-744 functions as either tumor suppressor or oncogene in the progression of a variety of tumors, with a tumor type-specific way. However, little is known about how miR-744 impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of microarray, qRT-PCR and re-analysis of MSKCC data, we found that CRPC tissues expressed much more miR-744 than ADPC tissues did, and the expression level of miR-744 was inversely associated with survival of CRPC patients. In vitro studies revealed that miR-744 promotes PCa cells proliferation, enhances migration, invasion; in vivo results demonstrated that silencing of miR-744 mediated by shRNA dramatically reduces PCa xenograft tumor growth. Importantly, through human gene expression array, pathway enrichment analysis and Western blot, we identified that miR-744 dramatically activated Wnt/?-catenin pathway by targeting multiple negative regulators of Wnt/?-catenin signaling, including SFRP1, GSK3?, TLE3 and NKD1. At molecular level, we further defined that NKD1 is a major functional target of miR-744. Our findings indicate that miR-744 acts as one of oncogenic factor in the progression of CRPC by recruiting a mechanism of aberrant activation of Wnt/?-catenin signaling.

SUBMITTER: Guan H 

PROVIDER: S-EPMC5362436 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature