title: miR-136 modulates TGF-β1-induced proliferation arrest by targeting PPP2R2A in keratinocytes.
abstract: Keratinocytes proliferation is critical for the capacity to heal wounds and accumulating evidences have proved that dysregulation of microRNAs is involved in proliferation of keratinocytes. However, the molecular mechanisms remain to be completely elucidated. Here, we show that miR-136 was significantly decreased by TGF-β1 treatment in HaCaT cells and normal human epidermal keratinocytes (NHEK), and it was a Smad3-dependent manner. By cell proliferation assay and cell cycle analysis, we found that reintroduction of miR-136 by transfection, as well as PPP2R2A silencing, counteracted TGF-β-induced proliferation arrest in HaCaT cells. Further, PPP2R2A was verified as a direct target of miR-136 by dual-luciferase reporter assays and Western blotting. These data suggest that miR-136 may play an important role during TGF-β1-induced proliferation arrest by targeting PPP2R2A in keratinocytes, which might represent a potential target for improving skin wound healing.
authors: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors: Dianbao
authors: 0000-0001-7063-7742
authors: D
authors: Zhang
authors: Department of Anus & Intestine Surgery, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors: Jing
authors: J
authors: Wang
authors: Department of Blood Transfusion, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors: Zhe
authors: Z
authors: Wang
authors: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors: Tao
authors: T
authors: Zhang
authors: Department of General Practice, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors: Ping
authors: P
authors: Shi
authors: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors: Xiliang
authors: X
authors: Wang
authors: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors: Feng
authors: F
authors: Zhao
authors: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors: Xiaoyu
authors: X
authors: Liu
authors: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors: Xuewen
authors: X
authors: Lin
authors: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors: Xining
authors: X
authors: Pang
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D000078404:Epidermal Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D055815:Young Adult
chemical_list: C577037:MIRN136 microRNA, human; D035683:MicroRNAs; C512974:PPP2R2A protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D054648:Protein Phosphatase 2
references: Tumour Biol. 2014 Jan;35(1):631-40
references: 23959478
references: Cell Death Differ. 2010 Feb;17(2):229-35
references: 19609273
references: Wound Repair Regen. 2009 Mar-Apr;17(2):153-62
references: 19320882
references: J Cell Physiol. 2010 Nov;225(2):310-5
references: 20568222
references: J Biol Chem. 2010 Sep 24;285(39):29863-73
references: 20663872
references: Cell Death Differ. 2008 Jul;15(7):1187-95
references: 18483491
references: Nat Cell Biol. 2010 Sep;12(9):886-93
references: 20711181
references: J Invest Dermatol. 2010 May;130(5):1249-57
references: 20090763
references: Development. 2008 Sep;135(17):2927-37
references: 18697906
references: Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6976-81
references: 20308562
references: Trends Cell Biol. 2009 Aug;19(8):385-94
references: 19648010
references: PLoS One. 2010;5(10):e13599
references: 21049042
references: J Dermatol Sci. 2010 May;58(2):97-104
references: 20399617
references: J Virol. 2010 Aug;84(15):7892-7
references: 20484493
references: J Cell Biol. 2008 Jan 28;180(2):273-84
references: 18209104
references: J Dent Res. 2010 Mar;89(3):219-29
references: 20139336
references: FEBS Lett. 2012 Oct 19;586(20):3608-12
references: 22967897
references: Genes Cancer. 2012 Nov;3(11-12):739-48
references: 23634261
references: Cell Death Dis. 2012;3:e435
references: 23190607
references: J Invest Dermatol. 2011 Jul;131(7):1521-9
references: 21412257
references: J Biol Chem. 2013 Jun 28;288(26):18911-22
references: 23720758
references: J Cell Sci. 2003 Aug 1;116(Pt 15):3227-38
references: 12829742
references: J Eur Acad Dermatol Venereol. 2013 May;27(5):531-5
references: 23030703
references: Cell Signal. 2014 Jul;26(7):1427-36
references: 24613410
references: Development. 2012 Apr;139(8):1405-16
references: 22434867