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miR-29a-3p/COL5A2信号轴对胃癌细胞耐药性的影响
作者:张帆  姜津霞  方向明 
单位:武汉科技大学附属武汉普仁医院 消化内科, 湖北 武汉 430080
关键词:胃癌 miR-29a-3p 胶原蛋白Ⅴ型2链 化疗耐药性 
分类号:R735.2
出版年·卷·期(页码):2021·49·第四期(369-376)
摘要:

目的:探究miR-29a-3p与胶原蛋白Ⅴ型2链(COL5A2)的靶向作用关系,以及它们对胃癌细胞MKN-28阿霉素耐药性的影响。方法:通过数据库查询胃癌组织中COL5A2的表达水平与癌症不同分期以及预后的相关性;检测miR-29a-3p在胃癌组织中的表达,并利用双荧光素酶报告基因分析COL5A2与miR-29a-3p的靶向关系;将miR-29a-3p mimics/inhibitor转染胃癌MKN-28细胞,利用不同浓度阿霉素处理,四甲基偶氮唑盐微量酶反应比色法检测细胞活力,并观察其对相关耐药蛋白的影响。结果:胃癌组织中COL5A2的表达水平显著高于正常组织(P<0.01),且随着肿瘤进展COL5A2表达增加,患者生存预后较差;荧光素酶报告结果显示miR-29a-3p靶向抑制COL5A2表达;MKN-28转染miR-29a-3p mimics和miR-29a-3p inhibitor后,与对照组相比miR-29a-3p mimics组细胞活力降低,COL5A2表达降低(P<0.05),相关耐药蛋白Pgp、MDRA1、HSP、GST表达下降(P<0.05);miR-29a-3p inhibitor组COL5A2表达增加(P<0.05),耐药蛋白Pgp、MDRA1、HSP、GST表达增加(P<0.05)。结论:与正常组织相比胃癌组织中COL5A2高表达,且随着癌症进展COL5A2表达增加,患者预后较差;miR-29a-3p能够通过靶向下调COL5A2的表达降低胃癌细胞MKN-28对阿霉素的耐药性。

Objective: To investigate the effect of miR-29a-3p and COL5A2 targeting on the resistance MKN-28 to doxorubicin.Methods: The online database was used to query the correlation between the expression level of COL5A2 mRNA in gastric cancer tissues and different stages, and prognosis of patients. The expression of miR-29a-3p in gastric cancer tissues was detected, and the relationship between COL5A2 and miR-29a-3p was analyzed by using luciferase reporter. miR-29a-3p mimics/inhibitor was transfected into gastric cancer MKN-28 cells. The western blottting was used to observe miR-29a-3p effect on related drug resistance genes.Results: The level of COL5A2 in gastric cancer tissues was significantly higher than that in normal tissues(P<0.01), and as the tumor progressed, the expression of COL5A2 increased, and the survival prognosis of the patient was poor; The luciferase report showed that miR-29a-3p directly induced COL5A2 expression. After transfection of miR-29a-3p mimics and miR-29a-3p inhibitor into MKN-28 cell, the expression of COL5A2 and cell activity in miR-29a-3p mimics group werereduced(P<0.05), and the expressions of drug resistance related proteins Pgp, MDRA1, HSP, GST decreased(P<0.05). While, the expressions of COL5A2 andPgp,MDRA1, HSP, and GST protein increased in miR-29a-3p inhibitor(P<0.05).Conclusion: Compared with normal tissues, COL5A2 is highly expressed in gastric cancer tissues, and presaged the poor prognosis of gastric cancer patient. miR-29a-3p can reducethe resistance of doxorubicin in MKN-28 through inhibiting the expression of COL5A2.

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