miR-21在结肠癌细胞失巢凋亡调节中的作用及机制研究  

Role and possible mechanism of miR-21 on the regulation of anoikis resistance in human colon carcinoma

作　　者：黄体政[1] 孙鹤[1] 肖军[2] Huang Tizheng;Sun He;Xiao Jun(Department of Gastroenterology,Hubei Aerospace Hospital;Department of Gastroenterology,Zhongnan Hospital of Wuhan University)

机构地区：[1]湖北航天医院消化内科,孝感432000 [2]武汉大学中南医院消化内科,武汉430071

出　　处：《重庆医科大学学报》2020年第5期645-649,共5页Journal of Chongqing Medical University

摘　　要：目的:探讨miR-21在结肠癌细胞失巢凋亡调节中的作用及机制。方法:qRT-PCR检测30例结肠癌组织中的miR-21表达,并评估其与临床病理特征和预后的关系;利用结肠癌HT-29细胞及其失巢凋亡抵抗亚群HT-29/AR细胞探讨miR-21表达水平与失巢凋亡抗性的关系;Western blot检测PDCD4、PTEN蛋白表达水平变化,并利用双荧光素酶报告基因实验验证miR-21对其3’UTR的直接结合作用。结果:miR-21在结肠癌组织中的表达明显高于癌旁组织,且与肿瘤细胞分化程度、淋巴结转移状态及TNM分期显著相关,其高表达患者预后较差;与HT-29细胞相比,HT-29/AR细胞miR-21明显上调,且miR-21模拟物转染可以明显提高HT-29细胞的失巢凋亡抗性;Western blot及双荧光素酶报告基因实验证实miR-21可通过抑制PDCD4和PTEN蛋白表达水平增加结肠癌细胞的失巢凋亡抗性。结论:miR-21可通过靶向抑制PDCD4和PTEN表达参与人结肠癌细胞失巢凋亡的调控。Objective:To investigate the role and possible mechanism of miR-21 on the regulation of anoikis in human colon carci-noma.Methods:The expression level of miR-21 in 30 cases of colon cancer was examined by qRT-PCR,and its correlation with clinicopathologic features and prognosis was further analyzed.HT-29 cells and its derivative HT-29/AR(subpopulation of HT-29 cells that acquired resistance to anoikis)were used to explore the relationship between the expression of miR-21 and anoikis resis-tance.Western blot was used to detect changes of PDCD4 and PTEN,and dual-luciferase reporter assay was applied to verify the di-rect conjunction of miR-21 to its 3’UTR.Results:Expression of miR-21 in human colon carcinoma tissues was higher than that in adjacent tissues;was significantly correlated with poor differentiation,lymph node metastasis and TNM stage;patients with high ex-pression of miR-21 had poor prognosis.Compared with HT-29 cells,miR-21 expression in HT-29/AR cells was significantly in-creased and transfection of miR-21 mimics was able to promote the anoikis resistance of HT-29 cells.Western blot and dual-lu-ciferase reporter assay demonstrated that miR-21 was able to increase the anoikis resistance of colon carcinoma cells by inhibiting expression of PDCD4 and PTEN.Conclusion:The miR-21 can participate in regulating anoikis in human colon carcinoma cells by targeted inhibiting PDCD4 and PTEN.

关 键 词：MIR-21 结肠癌 失巢凋亡 PDCD4 PTEN 

分 类 号：R735.35[医药卫生—肿瘤]