Overexpression of miR-101 suppresses collagen synthesis by targeting EZH2 in hypertrophic scar fibroblasts
作者机构:Department of Burns and Cutaneous SurgeryXijing HospitalFourth Military Medical UniversityXi’anShaanxi710032China
出 版 物:《Burns & Trauma》 (烧伤与创伤(英文))
年 卷 期:2021年第9卷第1期
页 面:83-94页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:supported by the National Natural Science Foundation of China(81772071 to DHH)
主 题:Hypertrophic scars miR-101 EZH2 Collagen Fibroblasts Skin Collagen
摘 要:Background:MicroRNA-101(miR-101)is a tumor suppressor microRNA(miRNA)and its loss is associated with the occurrence and progression of various ***,the biological function and target of miR-101 in the pathogenesis of hypertrophic scars(HS)remains ***:We harvested HS and paired normal skin(NS)tissue samples from patients and cultured their fibroblasts(HSF and NSF,respectively).We used quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),enzyme-linked immunosorbent assays(ELISA)and Western blot analyses to measure mRNA levels and protein expression of miR-101,enhancer of zeste homolog 2(EZH2),collagen 1 and 3(Col1 and Col3)andα-smooth muscle actin(α-SMA)in different in vitro *** also used RNA sequencing to evaluate the relevant signaling pathways and bioinformatics analysis and dual-luciferase reporter assays to predict miR-101 *** utilized a bleomycin-induced fibrosis mouse model in which we injected miR-101 mimics to evaluate collagen deposition in ***:We found low expression of miR-101 in HS and HSF compared to NS and *** miR-101 decreased Col1,Col3 andα-SMA expression in *** detected high expression of EZH2 in HS and *** of EZH2 decreased Col1,Col3 andα-SMA in ***,miR-101 targeted the 3-untranslated region(3UTR)of EZH2,as indicated by the decreased expression of *** EZH2 rescued miR-101-induced collagen ***-101 mimics effectively suppressed collagen deposition in the bleomycin-induced fibrosis mouse ***:Our data reveal that miR-101 targets EZH2 in HS collagen production,providing new insight into the pathological mechanisms underlying HS formation.