title: Autoregulatory suppression of c-Myc by miR-185-3p.
abstract: The expression of the c-myc oncogene at both protein and mRNA levels is transient and begins to be turned off 3-6 h after growth stimulation of cultured cells. The exact mechanism(s) underlying this down-regulation of c-Myc remains incompletely understood. Here we report the identification of miR-185-3p as a novel feedback regulator of c-Myc. This microRNA (miRNA) was initially identified as one of the c-Myc target miRNA transcripts through analysis of RNA samples isolated from cells prior to and after serum stimulation and further verified by real-time PCR, luciferase reporter, and ChIP assays. Interestingly, overexpression of wild type, but not mutant, miR-185-3p decreased the protein, but not mRNA, level of c-Myc in a dose-dependent fashion and also drastically abated the serum induction of c-Myc level in human cancer cells by targeting the coding sequence of c-Myc mRNA, consequently suppressing c-Myc-mediated proliferation. A miR-185-3p inhibitor rescued the inhibition of c-Myc expression by endogenous miR-185-3p. Thus, our results unveil miR-185-3p as the first miRNA that monitors c-Myc levels via an autoregulatory feedback mechanism in response to serum stimulation.
authors.affiliation: Department of Biochemistry and Molecular Biology and the Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Liao
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C552431:MIRN185 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger