miR-181a-5p靶向CTDSPL基因调节TGF-β信号通路在胃肠道间质瘤发生、发展中的作用  

Effects of miR-181a-5p on the occurrence and development of gastrointestinal stromal tumor through targeting CTDSPL and regulating TGF-βsignaling pathway

作　　者：谢艳英[1] 李帅帅 王田 崔永辉[1] 许春进[1] Xie Yanying;Li Shuaishuai;Wang Tian;Cui Yonghui;Xu Chunjin(Digestive Internal Medicine,the First People’s Hospital of Shangqiu City,Shangqiu 476100,China)

机构地区：[1]商丘市第一人民医院消化内科,476100

出　　处：《中华内分泌外科杂志》2021年第2期164-170,共7页Chinese Journal of Endocrine Surgery

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20191504)。

摘　　要：目的探讨miR-181a-5p靶向羧基末端区域小磷酸化酶样蛋白(carboxy-terminal domainsmall phosphatase-like,CTDSPL)基因介导TGF-β信号通路对胃肠道间质瘤发生发展的影响。方法选择2016年1月至2019年12月于商丘市第一人民医院行手术治疗的胃肠道间质瘤(gastrointestinal stromal tumor,GIST)患者作为研究对象,术中取患者的肿瘤组织和癌旁正常组织。分析患者的临床病理资料;采用定量实时聚合酶联反应(quantitative real-time polymerase chain reaction,qRT-PCR)检测CTDSPL基因mRNA和miR-181a-5p的表达量;采用western blot法检测CTDSPL基因及TGF-β信号通路相关因子的蛋白表达水平。将人胃肠道间质瘤细胞系(GIST-T1)分别转染miR-181a-5p mimic、miR-181a-5p inhibitor和CTDSPL过表达载体。MTT检测各组细胞增殖活力,Transwell检测各组细胞侵袭,流式细胞术检测各组细胞凋亡。结果相对于癌旁组织,GIST患者的肿瘤组织中miR-181a-5p及TGF-β信号通路相关因子表达增强,CTDSPL表达被抑制。肿瘤大小、浸润深度和改良NIH分级与GIST肿瘤组织CTDSPL基因mRNA表达量有关(P均<0.05)。相对于Blank组,敲除miR-181a-5p或过表达CTDSPL能抑制癌细胞增殖活力和侵袭,诱导细胞凋亡,而miR-181a-5p mimic对GIST-T1细胞的作用能被CTDSPL过表达挽救。结论miR-181a-5p可通过下调CTDSPL基因表达水平,激活TGF-β信号通路促进GIST的发生、发展。Objective To explore the effects of miR-181a-5p on the occurrence and development of gastrointestinal stromal tumors(GIST)through targeting CTDSPL mediating TGF-βsignaling pathway.Methods Surgical treatment of GIST patients in the First People’s Hospital of Shangqiu City from Jan.2016 to Dec.2019 were selected as research objects,and tumor tissue and adjacent normal tissue were collected intraoperatively.The clinicopathological data of the patients were analyzed.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression of CTDSPL gene and miR-181a-5p expression.Western blot was used to detect the protein level of CTDSPL and TGF-βsignaling pathway related factors.Human gastrointestinal stromal tumor cell lines(GIST-T1)were transfected with miR-181a-5p mimic,miR-181a-5p inhibitor,or CTDSPL overexpression vector.MTT was used to detect cell proliferation activity,Transwell assay was utilized to detect cell invasion,flow cytometry was used to determine cell apoptosis in each group.Results Compared with adjacent tissues,expression of miR-181a-5p and TGF-βsignaling pathway related factors was activated while CTDSPL expression was inhibited.Tumor size,invasion depth and modified NIH grading were related to the mRNA expression level of CTDSPL gene in GIST tumor tissues(All P<0.05).Compared with Blank group,inhibition of miR-181a-5p or CTDSPL overexpression had the ability to inhibit the cell viability and invasion,induce apoptosis.The effects of miR-181a-5p mimic on GIST-T1 can be saved by CTDSPL overexpression.Conclusion miR-181a-5p can promote the occurrence and development of GIST by down-regulating the CTDSPL gene level and activating TGF-βsignaling pathway.

关 键 词：胃肠道间质瘤 miR-181a-5p CTDSPL TGF-Β信号通路 

分 类 号：R735.2[医药卫生—肿瘤]