miR-188-5p regulates proliferation and invasion via PI3K/Akt/MMP-2/9 signaling in keloids

查看全文 作　　者：Wenyan [1]Zhu;Xiaoyan [1]Wu;Bo [2]Yang;Xiaodong [1]Yao;Xiaomei [1]Cui;Pan [1]Xu;Xiaodong [1]Chen

机构地区：[1]Department of Medical Cosmetology & Dermatology,The Affiliated Hospital of Nantong University,Nantong 226001,China;[2]Department of Dermatology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China

出　　处：《Acta Biochimica et Biophysica Sinica》索引2019年第51卷第2期,共12页

基　　金：the grants from the National Natural Science Foundation of China(Nos.81473684 and 81041076);the Innovative Project of Nantong University Postgraduate Students(No.YKC15097). 摘　　要：Keloids(KDs)and hypertrophic scars(HSs),two forms of pathological scars,seriously affect the physical and psychological health of patients.Despite many similarities with HSs,KDs are characterized by invasion and a high rate of recurrence after surgery,features they share in common with tumors.The underlying molecular mechanisms of this phenomenon have not been fully elucidated.In this study,we used microRNA(miRNA)array analysis to search for invasion-associated miRNAs in KDs.The expression of miR-188-5p in KDs,HSs,normal skin(NS)tissues,and cell lines was measured by quantitative real-time polymerase chain reaction.Furthermore,cell proliferation,migration,and invasion were detected in KD fibroblasts(KFs)and HS fibroblasts(HSFs),and interrelated proteins were ascertained by western blot analysis.It was found that miR-188-5p was significantly decreased in KD tissue compared with HS and NS tissues.Upregulated expression of miR-188-5p suppressed KF proliferation,migration,and invasion;and decreased expression of miR-188-5p also promoted HSF proliferation,migration,and invasion.The protein levels of MMP-2,MMP-9,PI3K,and p-Akt in miR-188-5p mimic-transfected KFs were repressed.In contrast,after transfection with miR-188-5p inhibitor,the protein levels of MMP-2,MMP-9,PI3K,and p-Akt were higher than the control in HSFs.Treatment with PI3K/Akt inhibitor LY294002 in KFs with miR-188-5p inhibitor did not further reduce their proliferation,migration,and invasion.The upregulation of MMP-2 and MMP-9 by miR-188-5p inhibitor could be abolished by LY294002.These findings together demonstrate a tumor-suppressive role of miR-188-5p in KD proliferation and invasion via PI3K/Akt/MMP-2/9 signaling,indicating that miR-188-5p may be a potential prognostic marker and therapeutic target for KDs. 关键词：KELOID miR-188-5p INVASION MMP PI3K/AKT

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miR-188-5p regulates proliferation and invasion via PI3K/Akt/MMP-2/9 signaling in keloids

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