title: miR-181a shows tumor suppressive effect against oral squamous cell carcinoma cells by downregulating K-ras.
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.
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA 90095, USA. kshin@dentistry.ucla.edu
authors.forename: Ki-Hyuk
authors.initials: KH
authors.lastname: Shin
authors.forename: Susan D
authors.initials: SD
authors.lastname: Bae
authors.forename: Hannah S
authors.initials: HS
authors.lastname: Hong
authors.forename: Reuben H
authors.initials: RH
authors.lastname: Kim
authors.forename: Mo K
authors.initials: MK
authors.lastname: Kang
authors.forename: No-Hee
authors.initials: NH
authors.lastname: Park
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D011905:Genes, ras; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs