基于生物信息学探究miR-17-5p促进三阴性乳腺癌增殖迁移的机制  

Mechanism of miR-17-5p promoting the proliferation and migration of triple-negative breast cancer based on bioinformatics

作　　者：贺鑫 陈芳芳[1] 龚鹏举 宋文静 杨燕 钱晨 何浩东 张京伟[1] HE Xin;CHEN Fangfang;GONG Pengju;SONG Wenjing;YANG Yan;QIAN Chen;HE Haodong;ZHANG Jingwei(Dept.of Breast and Thyroid Surgery,Zhongnan Hospital of Wuhan University,Hubei Key Laboratory of Tumor Biological Behaviors,&Hubei Cancer Clinical Study Center,Wuhan 430071,Hubei,China;Dept.of Pathophysiology,Wuhan University School of Basic Medical Sciences,Wuhan 430071,Hubei,China)

机构地区：[1]武汉大学中南医院甲乳外科/湖北省肿瘤生物学行为重点实验室/湖北省肿瘤医学临床研究中心,湖北武汉430071 [2]武汉大学基础医学院病理生理学教研室,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2022年第5期755-761,共7页Medical Journal of Wuhan University

基　　金：武汉大学中南医院医学科技创新平台建设支撑项目(编号:PTXM2020031)。

摘　　要：目的:探究miR-17-5p对三阴性乳腺癌(TNBC)增殖迁移的调控作用及对患者预后的影响。方法:下载TCGA数据库中乳腺癌microRNA表达谱数据和临床病理资料,通过差异分析及Kaplan Meier生存分析,筛选TNBC预后相关microRNA。实时荧光定量PCR检测不同类型乳腺癌细胞系中miR-17-5p的表达水平,CCK-8、划痕实验检测miR-17-5p对TNBC细胞增殖及迁移能力的影响。Starbase数据库预测miR-17-5p靶基因,Metascape及STRING数据库对靶基因进行功能及信号通路聚类分析,并构建蛋白质-蛋白质相互作用网络,进而筛选下游关键调控机制。结果:TNBC中共有98个microRNA特异性表达上调,其中miR-17-5p在TNBC中表达高于非TNBC和正常组织(P<0.001),且与不良预后相关。miR-17-5p在TNBC细胞系中表达特异性升高,过表达miR-17-5p后TNBC细胞增殖及迁移能力显著增强,而抑制miR-17-5p表达后细胞增殖及迁移能力减弱。生物信息学分析筛选出407个miR-17-5p下游潜在靶基因及肿瘤相关的分子机制,其中FBXL5在TNBC中的低表达与患者预后不良密切相关(P<0.05),且miR-17-5p与FBXL5的mRNA表达水平显著负相关。结论:miR-17-5p在TNBC中发挥着致癌基因的作用,可通过调控肿瘤相关通路促进TNBC的发生发展,从而影响患者的预后。Objective: To investigate the role of miR-17-5p on the proliferation and migration of triple-negative breast cancer(TNBC) and its impact on patients’ prognosis. Methods: microRNA expression profile and clinicopathological data of breast cancer from TCGA(The Cancer Genome Atlas) database were downloaded to screen prognosis-related microRNAs in TNBC by differential analysis and Kaplan Meier survival analysis. miR-17-5p expression levels in different types of breast cancer cell lines were detected by real-time fluorescence quantitative PCR. CCK-8 and scratch assay were used to detect the effect of miR-17-5p on the proliferation and migration ability of TNBC cells. The Starbase database was used to predict miR-17-5p target genes, and the Metascape and STRING databases were used for functional and signaling pathway clustering analysis, constructing protein-protein interaction networks and screening for key downstream regulatory mechanisms. Results: A total of 98microRNAs were specifically upregulated in TNBC. miR-17-5p was more expressed in TNBC than in non-TNBC and normal breast tissues(P<0. 001) and was associated with poor prognosis. miR-17-5p was specifically elevated in TNBC cell lines, and overexpression of miR-17-5p increased the proliferation and migration ability of TNBC cells, while the proliferation and migration ability of cells were reduced by inhibition of miR-17-5p. 407 downstream potential target genes and tumor-related molecular mechanisms of miR-17-5p were found, among which low expression of FBXL5 in TNBC was closely associated with poor prognosis(P<0. 05), and the expression level of miR-17-5p was significantly negatively correlated FBXL5. Conclusion: miR-17-5p plays an oncogenic role in TNBC and can promote the development of TNBC by regulating tumor-associated pathways, thus affecting the prognosis of patients.

关 键 词：miR-17-5p 三阴性乳腺癌 增殖 迁移 调控机制 

分 类 号：R737.9[医药卫生—肿瘤]