摘要
[目的]通过联合miRNA芯片与蛋白组学技术考察创伤性股骨头坏死(TI0NFH)患者外周血特异性miRNAs调控的差异化蛋白,旨在探讨TI0NFH的表观遗传机制。[方法]在前期TI0NFH转录组学的基础上,通过三个数据库对已筛选并验证的8个特异性miRNAs进行靶基因预测;通过蛋白组学技术筛选出差异表达蛋白;将miRNAs靶基因与蛋白组结果进行关联分析。[结果]上调miRNAs的靶基因共有609个,下调miRNAs的靶基因共有37个;蛋白组学鉴定出共115个显著差异表达的蛋白分子(P<0.05)。蛋白组和miRNA数据关联分析表明:hsa-miR-7i-5p、hsa-miR-16-2-3p、hsa-miR-320a和hsa-miR-93-5p共同祀向的VDAC1分子,hsa-miR-16-2-3p和hsa-miR-25-3p共同祀向的PSMD14分子,hsa-miR-7i-5p和hsa-miR-320a共同靶向的PRPS14分子,以及hsa-miR-25-3p靶向的MPP1分子,差异均有统计学意义(P<O.O5);这些miRNAs对破骨细胞分化、PI3K-Akt等信号通路具有调控作用。[结论]Hsa-miR-7i-5p、hSa-miR-16-2-3p等特异性miRNAs可能通过影响VDAC1、PSMD14、MPP1、PRPS1等蛋白表达以及体内相关信号通路,共同参与TI0NFH的表观遗传机制。
[Objective]To further reveal the epigenetic mechanism of trauma-induced osteonecrosis of the femoral head(TIONFH),the differential proteins regulated by specific miRNAs in peripheral blood of patients with TIONFH were investigated through combination with miRNA microchips and proteomics.[Methods]On the basis of preliminary miRNA data of TIONFH,target genes of 8 specific miRNAs screened and verified were predicted by three databases.Differentially expressed proteins were screened out by proteomics.The target genes of miRNAs were correlated with differentially expressed proteins in the proteome.[Results]There were 609 upregulated target genes and 37 down-regulated target genes;115 significantly differentially expressed proteins were identified by proteomics(P<0.05).Correlation analysis of proteomic and miRNA data showed that hsa-miR-7i-5p,hsa-miR-16-2-3p,hsa-miR-320a and hsa-miR-93-5p worked together to target VDAC1,hsa-miR-16-2-3p and hsa-miR-25-3p targeted PSMD14 together,hsa-miR-7i-5p and hsa-miR-320a targeted PRPS together,and the MPP1 was targeted by hsa-miR-25-3p.Above four proteins were significantly different(P<0.05).These miRNAs could affect osteoclast differentiation and PI3K-AKT signaling pathway and so on.[Conclusions]Hsa-miR-7i-5p,hsa-miR-16-2-3p and other specific miRNAs can regulate VDAC1,PSMD14,MPP1,PRPS1 and other proteins,as well as related signaling pathways,jointly participating in the epigenetic mechanism of TIONFH.
作者
黄世金
张颖
韩超
刘成业
秦崇臻
卢瑶瑶
柴玉娜
HUANG Shi-jin;ZHANG Ying;HAN Chao;LIU Cheng-ye;QIN Chong-zhen;LU Yao-yao;CHAI Yu-na(Department of Orthopedics,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Hip Disease Research and Treatment Center,Luoyang Orthopedic Hospital,Luoyang 471002,China;Department of Orthopedics,The Third Affiliated Hospital,Henan University of Science and Technology,Luoyang Dongfang Hospital,Luoyang 471003,China;The Academy of Medicine Science,Zhengzhou University,Zhengzhou 450003,China)
出处
《中国矫形外科杂志》
CAS
CSCD
北大核心
2021年第19期1784-1788,共5页
Orthopedic Journal of China
基金
国家自然科学基金资助项目(编号:81703955,81703780)
河南省科技攻关计划项目(编号:202102310510)
郑州大学第一附属医院青年基金资助项目(编号:YNQN2017036)。