title: Mir-509-5p joins the Mdm2/p53 feedback loop and regulates cancer cell growth.
abstract: Although the Mdm2/p53 interaction has been well documented, it is not clear whether there are new microRNAs participating in this regulatory network. Here, we provide evidence that miR-509-5p, which is downregulated in a subset of newly diagnosed cervical cancer and hepatocellular carcinoma tissues compared with the adjacent nontumor tissue, can be activated by p53 through binding the promoter of miR-509-5p and it suppresses the growth and invasion/migration of cervical cancer and hepatoma cells by regulating apoptosis and the G1/S-phase transition of cell cycle. Furthermore, Mdm2 was identified to be a target of miR-509-5p by targeting its 3'-UTR. Restoration of Mdm2 abrogated the cell phenotypes induced by miR-509-5p. Moreover, ectopic expression of miR-509-5p in HeLa and QGY-7703 cells repressed the expression of Mdm2, subsequently enhancing its p53-activating effects. These results suggest that miR-509-5p is a new regulator of Mdm2/p53 pathway and may play a key role in cancer development.
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Ren
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Nong
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Y-R
authors.initials: YR
authors.lastname: Lv
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: H-H
authors.initials: HH
authors.lastname: Sun
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: P-P
authors.initials: PP
authors.lastname: An
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: H
authors.initials: H
authors.lastname: Tang
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D059585:G1 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D016415:Sequence Alignment; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2