title: miR-19b promotes tumor growth and metastasis via targeting TP53.
abstract: Tumor suppressor TP53 (or p53) is one of the most important regulators in numerous physiological and pathological processes. Recently, the miRNA-mediated post-transcription regulation of p53 has been studied. However, systematic studies of miRNA targeting sites within the p53 gene are still a challenging task. Here, we developed a dual-color assay capable of identifying miRNA targeting sites in a certain gene, specifically p53, in a simple, direct, and robust manner. Results showed that p53 was a direct and critical target of miR-19b, but not miR-19a, regardless of sequence similarity. Overexpression of miR-19b observed in human cancer cells can diminish p53 protein levels and, subsequently, downstream components such as Bax and p21. This miR-19b-mediated p53 reduction was shown to promote cell cycle, cell migration or invasion, and repress senescence and apoptosis in vitro. Further investigation revealed that miR-19b controls tumor growth and metastasis in vivo. Therefore, it is possible that miR-19b antagomirs or sponges could be developed as therapeutic agents against tumor development.
authors.affiliation: Biomedical Engineering Department, College of Engineering.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Biomedical Engineering Department, College of Engineering.
authors.forename: Shenyi
authors.initials: S
authors.lastname: Yin
authors.affiliation: Biomedical Engineering Department, College of Engineering.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Biomedical Engineering Department, College of Engineering.
authors.forename: Junyu
authors.initials: J
authors.lastname: Yang
authors.affiliation: Biomedical Engineering Department, College of Engineering.
authors.forename: Hanshuo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Biomedical Engineering Department, College of Engineering.
authors.forename: Changhong
authors.initials: C
authors.lastname: Sun
authors.affiliation: Biomedical Engineering Department, College of Engineering.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: Biomedical Engineering Department, College of Engineering.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Biomedical Engineering Department, College of Engineering State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.
authors.forename: Jianzhong Jeff
authors.initials: JJ
authors.lastname: Xi
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein
keywords: TP53; miRNA; tumor metastasis
references.citation: Nature. 2009 Nov 5;462(7269):104-7
references.pmid: 19847165
references.citation: Nucleic Acids Res. 2012 Sep;40(16):8048-58
references.pmid: 22684508
references.citation: Genes Dev. 2009 Apr 1;23(7):862-76
references.pmid: 19293287
references.citation: RNA. 2008 Sep;14(9):1720-9
references.pmid: 18697919
references.citation: Nature. 1991 Jun 6;351(6326):453-6
references.pmid: 2046748
references.citation: Oncogene. 2011 Feb 17;30(7):843-53
references.pmid: 20935678
references.citation: Mol Cell Biol. 2000 May;20(10):3705-14
references.pmid: 10779360
references.citation: Nat Rev Mol Cell Biol. 2008 Sep;9(9):702-12
references.pmid: 18719709
references.citation: Mol Biol Cell. 2001 Aug;12(8):2229-44
references.pmid: 11514613
references.citation: J Immunol. 2012 Jan 1;188(1):454-61
references.pmid: 22105995
references.citation: Mol Cell. 2010 Jun 11;38(5):689-99
references.pmid: 20542001
references.citation: Cancer Lett. 2012 Sep 28;322(2):148-58
references.pmid: 22561557
references.citation: Science. 1991 Jul 5;253(5015):49-53
references.pmid: 1905840
references.citation: Science. 2004 Feb 13;303(5660):1010-4
references.pmid: 14963330
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: EMBO J. 2006 Jun 7;25(11):2615-22
references.pmid: 16757976
references.citation: EMBO J. 2009 Sep 16;28(18):2719-32
references.pmid: 19696742
references.citation: Iran J Med Sci. 2012 Mar;37(1):3-8
references.pmid: 23115424
references.citation: Nat Neurosci. 2008 Oct;11(10):1137-9
references.pmid: 18758459
references.citation: PLoS Genet. 2010 Jan;6(1):e1000795
references.pmid: 20062521
references.citation: Nat Cell Biol. 2010 Oct;12(10):993-8
references.pmid: 20818388
references.citation: Oncogene. 2000 Nov 2;19(46):5259-69
references.pmid: 11077443
references.citation: J Pathol. 1999 Jan;187(1):8-18
references.pmid: 10341702
references.citation: Nat Cell Biol. 2008 Jun;10(6):676-87
references.pmid: 18454141
references.citation: Genes Dev. 2009 Dec 15;23(24):2839-49
references.pmid: 20008935