Qian Sun1, Xian Zhao, Xin Liu, Yanli Wang, Jian Huang, Bing Jiang, Qin Chen, Jianxiu Yu. 1. Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract
BACKGROUND: miR-146a (miR-146a-5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR-146a in prostate cancer is still limited. METHODS: The expression levels of miR-146a in cell lines and tissues were measured by qRT-PCR and in situ hybridization. Effects of miR-146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR-146a and the 3'UTR of potential targets. RESULTS: We found that enforced over-expression of miR-146a in prostate cancer cells suppressed whereas knockdown of miR-146a increased anchorage-independent growth, migration, and invasion. Mechanistic studies revealed that miR-146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti-migration effect of overexpressing miR-146a, and knockdown of Rac1 in miR-146a-silencing cells antagonized the increase in cell motility induced by silencing miR-146a. Furthermore, miR-146a was found to be inversely correlated with Rac1 in human prostate cancer tissues. CONCLUSIONS: Our data suggest that miR-146a plays a suppressive role in prostate cancer through down-regulation of Rac1. The miR-146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression.
BACKGROUND:miR-146a (miR-146a-5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR-146a in prostate cancer is still limited. METHODS: The expression levels of miR-146a in cell lines and tissues were measured by qRT-PCR and in situ hybridization. Effects of miR-146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR-146a and the 3'UTR of potential targets. RESULTS: We found that enforced over-expression of miR-146a in prostate cancer cells suppressed whereas knockdown of miR-146a increased anchorage-independent growth, migration, and invasion. Mechanistic studies revealed that miR-146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti-migration effect of overexpressing miR-146a, and knockdown of Rac1 in miR-146a-silencing cells antagonized the increase in cell motility induced by silencing miR-146a. Furthermore, miR-146a was found to be inversely correlated with Rac1 in humanprostate cancer tissues. CONCLUSIONS: Our data suggest that miR-146a plays a suppressive role in prostate cancer through down-regulation of Rac1. The miR-146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression.
Authors: Cornelia Lerner; Silke Wemmert; Florian Bochen; Philipp Kulas; Maximilian Linxweiler; Andrea Hasenfus; Joana Heinzelmann; Petra Leidinger; Christina Backes; Eckart Meese; Steffi Urbschat; Bernhard Schick Journal: J Cancer Res Clin Oncol Date: 2015-11-30 Impact factor: 4.553
Authors: Laura Beth Moore; Andrew J Sawyer; Jennifer Saucier-Sawyer; W Mark Saltzman; Themis R Kyriakides Journal: Biomaterials Date: 2016-02-26 Impact factor: 12.479