Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 44, Issue 9, Pages 1465-1472Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2012.05.015
Keywords
MicroRNA; miR-139; RAP1B; Colorectal carcinoma; Tumour suppressor
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Funding
- National Natural Science Foundation of China [81101515, 30973663]
- Program of Shanghai Municipal Education Commission [12YZ052, shjdy027]
- Shanghai Municipal Health Bureau [2011Y189]
- National Key Program for Basic Research of China [2010CB529902]
- Science and Technology Commission of Shanghai [10JC1409100]
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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, LS174T, 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. (C) 2012 Elsevier Ltd. All rights reserved.
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