MiR-760通过抑制钙离子信号关键分子干预结肠癌转移的研究  

Effect of MiR-760 on Colon Cancer Metastasis by Inhibiting the Key Molecules of Calcium Ion Signal

作　　者：王晓元[1] 赵轶峰[1] 杨永江[1] 黄迪[1] 苏卓彬[1] 李坤[2] 李晶晶 李曙光[1] WANG Xiaoyuan;ZHAO Yifeng;YANG Yongjiang;HUANG Di;SU Zhuobin;LI Kun;LI Jingjing;LI Shuguang(Department of Gastrointestinal Tumor Surgery,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei Province,075000;Department of Pathology,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei Province,075000)

机构地区：[1]河北北方学院附属第一医院胃肠肿瘤外科,075000 [2]河北北方学院附属第一医院病理科,075000

出　　处：《胃肠病学》2020年第6期332-338,共7页Chinese Journal of Gastroenterology

基　　金：2019年度河北省医学课题研究计划(20190914)。

摘　　要：背景:微小RNA(miRNA)是一种新的癌症治疗相关的生物学标志物,研究表明miR-760在结直肠癌的发生、发展中起有重要作用。目的:探讨miR-760对结肠癌细胞增殖、周期、迁移和侵袭的调控作用及其机制。方法:采用qRT-PCR法检测结肠癌组织以及结肠癌细胞株HCT116、HT29、SW480和SW620中miR-760表达。双萤光素酶报告基因实验验证miR-760与STIM1的靶向关系。以蛋白质印迹法、免疫组化染色分别检测结肠癌细胞和组织中STIM1蛋白表达,CCK-8法检测细胞增殖能力,流式细胞术检测细胞周期,Transwell实验检测细胞迁移、侵袭。构建结肠癌裸鼠移植瘤模型并观察miR-760对肿瘤生长的影响。结果:MiR-760在结肠癌组织和结肠癌细胞中的表达均明显降低,而STIM1在结肠癌组织和细胞中高表达。MiR-760通过与STIM1的3’-UTR互补结合抑制其表达。过表达miR-760能抑制结肠癌细胞增殖,阻滞S期,抑制细胞迁移和侵袭,但上调STIM1能逆转这种抑制效果。在结肠癌裸鼠移植瘤模型中,过表达miR-760能下调STIM1表达并抑制肿瘤生长。结论:MiR-760通过靶向STIM1参与对结肠癌细胞生物学行为的调控,在结肠癌中发挥抑癌的作用。Background:MicroRNAs(miRNAs)are considered as new biomarkers related to cancer treatment.Studies have shown that miR-760 plays an important role in the development of colorectal cancer.Aims:To investigate the regulatory effect and mechanism of miR-760 on proliferation,cycle,migration and invasion of colon cancer cells.Methods:qRT-PCR was used to detect the expression of miR-760 in colon cancer tissue and colon cancer cell lines HCT116,HT29,SW480 and SW620.The targeted relationship between miR-760 and STIM1 was verified by dual luciferase reporter gene test.Expression of STIM1 in colon cancer cells and tissue was detected by Western blotting and immunohistochemistry,respectively.CCK-8 assay was used to detect cell proliferation ability,flow cytometry was used to detect cell cycle,and Transwell assay was used to detect cell migration and invasion.The xenograft model of colon cancer in nude mice was constructed,and the effect of miR-760 on tumor growth was measured.Results:Expression of miR-760 was significantly decreased in colon cancer tissue and colon cancer cells,while expression of STIM1 was significantly increased in colon cancer tissue and colon cancer cells.MiR-760 inhibited expression of STIM1 by complementary binding to the 3’-UTR of STIM1.Overexpression of miR-760 inhibited colon cancer cell proliferation,S-phase arrest,migration and invasion,and up-regulation of STIM1 reversed the inhibitory effect.In the xenograft model of colon cancer in nude mice,overexpression of miR-760 down-regulated expression of STIM1 and inhibited tumor growth.Conclusions:MiR-760 is involved in the regulation of biological behavior of colon cancer cells by targeting STIM1,and plays a role in tumor inhibition of colon cancer.

关 键 词：结肠肿瘤 MiR-760 STIM1 细胞增殖 细胞凋亡 细胞迁移 细胞侵袭 

分 类 号：R73[医药卫生—肿瘤]