title: Elevated miR-34c-5p mediates dermal fibroblast senescence by ultraviolet irradiation.
abstract: Previous studies showed that several miRNAs can regulate pathways involved in UVB-induced premature senescence and response to ultraviolet irradiation. It has also been reported that miR-34c-5p may be involved in senescence-related mechanisms. We propose that miR-34c-5p may play a crucial role in senescence of normal human primary dermal fibroblasts. Here, we explored the roles of miR-34c-5p in UVB-induced premature senescence on dermal fibroblasts. MiR-34c-5p expression was increased in dermal fibroblasts after repeated subcytotoxic UVB treatments. Underexpression of miR-34c-5p in dermal fibroblasts led to a marked delay of many senescent phenotypes induced by repeated UVB treatments. Furthermore, underexpression of miR-34c-5p in dermal fibroblasts can antagonize the alteration of G1-arrested fibroblasts. Moreover, E2F3, which can inactivate p53 pathway and play a role in cell cycle progression, is a down-stream target of miR-34c-5p. Forced down-expression of miR-34c-5p decreased the expression of UVB-SIPS induced P21 and P53 at both mRNA and protein levels. Our data demonstrated that down-regulation of miR-34c-5p can protect human primary dermal fibroblasts from UVB-induced premature senescence via regulations of some senescence-related molecules.
authors: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Guangzhou road 300#, Nanjing, Jiangsu province, China PR.
authors: Bing-rong
authors: BR
authors: Zhou
authors: Xian-fei
authors: XF
authors: Guo
authors: Jia-an
authors: JA
authors: Zhang
authors: Yang
authors: Y
authors: Xu
authors: Wei
authors: W
authors: Li
authors: Di
authors: D
authors: Wu
authors: Zhi-qiang
authors: ZQ
authors: Yin
authors: Felicia
authors: F
authors: Permatasari
authors: Dan
authors: D
authors: Luo
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000528:radiation effects*; D002648:Child; D015536:Down-Regulation; D050699:E2F3 Transcription Factor / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014466:Ultraviolet Rays; D054462:p21-Activated Kinases / Q000096:biosynthesis
chemical_list: D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D054462:p21-Activated Kinases
keywords: UVB; human skin fibroblasts.; miR-34c-5p; premature senescence
references: Exp Gerontol. 2003 Nov-Dec;38(11-12):1265-70
references: 14698806
references: Nature. 2001 Nov 22;414(6862):457-62
references: 11719808
references: Genes Dev. 1999 Jun 15;13(12):1501-12
references: 10385618
references: Biochim Biophys Acta. 2009 Apr;1792(4):341-52
references: 19419692
references: Int J Biochem Cell Biol. 2002 Nov;34(11):1331-9
references: 12200029
references: Arch Dermatol Res. 2012 Apr;304(3):223-8
references: 22350182
references: Clin Cancer Res. 2010 Feb 15;16(4):1119-28
references: 20145172
references: Exp Dermatol. 2012 Apr;21(4):317-9
references: 22417313
references: Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):527-31
references: 12515865
references: J Cell Sci. 2012 Dec 15;125(Pt 24):6117-26
references: 23038777
references: Mech Ageing Dev. 2009 Nov-Dec;130(11-12):731-41
references: 19782699
references: Cell Death Differ. 2010 Feb;17(2):193-9
references: 19461653
references: Cancer Res. 2008 May 1;68(9):3193-203
references: 18451145
references: Cell Stress Chaperones. 2008 Dec;13(4):447-58
references: 18465208
references: Mol Cell Biol. 2007 Jan;27(1):65-78
references: 17167174
references: J Biol Chem. 2006 Nov 24;281(47):36124-31
references: 17008321
references: Nature. 2007 Jun 28;447(7148):1130-4
references: 17554337
references: Micron. 2004;35(3):155-9
references: 15036269
references: J Pharm Pharmacol. 2006 Dec;58(12):1577-83
references: 17331320
references: Hepatology. 2012 Jul;56(1):186-97
references: 22318941
references: Cancer Chemother Pharmacol. 2013 May;71(5):1159-71
references: 23423488
references: Clin Geriatr Med. 2001 Nov;17(4):617-30, v
references: 11535419
references: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9740-4
references: 15210942