miR-181a shows tumor suppressive effect against oral squamous cell carcinoma cells by downregulating K-ras |
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| Authors: | Shin Ki-Hyuk Bae Susan D Hong Hannah S Kim Reuben H Kang Mo K Park No-Hee |
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| Institution: | aSchool of Dentistry, University of California, Los Angeles, CA 90095, United States;bDental Research Institute, University of California, Los Angeles, CA 90095, United States;cJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, United States;dDavid Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States |
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| Abstract: | MicroRNAs (miRNAs) are epigenetic regulators of gene expression, and their deregulation plays an important role in human cancer, including oral squamous cell carcinoma (OSCC). Recently, we found that miRNA-181a (miR-181a) was upregulated during replicative senescence of normal human oral keratinocytes. Since senescence is considered as a tumor suppressive mechanism, we thus investigated the expression and biological role of miR-181a in OSCC. We found that miR-181a was frequently downregulated in OSCC. Ectopic expression of miR-181a suppressed proliferation and anchorage independent growth ability of OSCC. Moreover, miR-181a dramatically reduces the growth of OSCC on three dimensional organotypic raft culture. We also identified K-ras as a novel target of miR-181a. miR-181a decreased K-ras protein level as well as the luciferase activity of reporter vectors containing the 3′-untranslated region of K-ras gene. Finally, we defined a minimal regulatory region of miR-181a and found a positive correlation between its promoter activity and the level of miR-181a expression. In conclusion, miR-181a may function as an OSCC suppressor by targeting on K-ras oncogene. Thus, miR-181a should be considered for therapeutic application for OSCC. |
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| Keywords: | miR-181a K-ras Tumor suppressor Oral cancer |
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