BACKGROUND: MicroRNAs (miRNAs) are strongly implicated in carcinogenesis, but their specific roles in the major cancers have yet to be fully elucidated. METHODS: The expression levels of miR-139 in colorectal carcinoma and paired normal tissues were examined using real-time PCR assays. Potential functions of miR-139 were evaluated in colorectal carcinoma cell lines (SW480, SW620, LS174 T, and HCT116) using miR-139 mimics, anti-miR-139, and siRNA RAP1B. RESULTS: In this study, we determined that miR-139 is down-regulated in colorectal carcinoma (CRC) tissues. Lower miR-139 expression correlates with more advanced CRC and lower overall survival of patients with CRC. The ectopic expression of miR-139 in human CRC cells decreased cell growth and tumorigenicity, whereas the silencing of miR-139 promoted cell growth. Mechanistic studies revealed that miR-139 repressed the activity of a reporter gene fused to the 3'-untranslated region of RAP1B, whereas miR-139 silencing up-regulated the expression of the reporter gene. RNAi-mediated knockdown of RAP1B phenocopied the antiproliferative effect of miR-139, whereas the overexpression of RAP1B blocked miR-139-mediated antiproliferative effects in CRC cells. CONCLUSIONS: Taken together, these results demonstrated that miR-139 decreases proliferation by directly targeting RAP1B, defining miR-139 as a new putative tumour suppressor miRNA in CRC.
BACKGROUND: MicroRNAs (miRNAs) are strongly implicated in carcinogenesis, but their specific roles in the major cancers have yet to be fully elucidated. METHODS: The expression levels of miR-139 in colorectal carcinoma and paired normal tissues were examined using real-time PCR assays. Potential functions of miR-139 were evaluated in colorectal carcinoma cell lines (SW480, SW620, LS174 T, and HCT116) using miR-139 mimics, anti-miR-139, and siRNA RAP1B. RESULTS: In this study, we determined that miR-139 is down-regulated in colorectal carcinoma (CRC) tissues. Lower miR-139 expression correlates with more advanced CRC and lower overall survival of patients with CRC. The ectopic expression of miR-139 in human CRC cells decreased cell growth and tumorigenicity, whereas the silencing of miR-139 promoted cell growth. Mechanistic studies revealed that miR-139 repressed the activity of a reporter gene fused to the 3'-untranslated region of RAP1B, whereas miR-139 silencing up-regulated the expression of the reporter gene. RNAi-mediated knockdown of RAP1B phenocopied the antiproliferative effect of miR-139, whereas the overexpression of RAP1B blocked miR-139-mediated antiproliferative effects in CRC cells. CONCLUSIONS: Taken together, these results demonstrated that miR-139 decreases proliferation by directly targeting RAP1B, defining miR-139 as a new putative tumour suppressor miRNA in CRC.
Authors: Louis A Saddic; Tzuu-Wang Chang; Martin I Sigurdsson; Mahyar Heydarpour; Benjamin A Raby; Stanton K Shernan; Sary F Aranki; Simon C Body; Jochen D Muehlschlegel Journal: Physiol Genomics Date: 2015-07-14 Impact factor: 3.107
Authors: Heidi Dvinge; Anna Git; Stefan Gräf; Mali Salmon-Divon; Christina Curtis; Andrea Sottoriva; Yongjun Zhao; Martin Hirst; Javier Armisen; Eric A Miska; Suet-Feung Chin; Elena Provenzano; Gulisa Turashvili; Andrew Green; Ian Ellis; Sam Aparicio; Carlos Caldas Journal: Nature Date: 2013-05-05 Impact factor: 49.962