miR-134-5p靶向抑制PAK3表达增强多发性骨髓瘤细胞的化疗敏感性的研究  

Study of miR-134-5p Enhances Chemosensitivity in Multiple Myeloma Cells by Inhibiting Expression of PAK3

作　　者：袁瑞丽[1] 柳娟 刘妮 赵娜[1] 尹晶晶[1] 郭炫[1] YUAN Rui-li;LIU Juan;LIU Ni;ZHAO Na;YIN Jing-jing;GUO Xuan(Department of Laboratory Medicine,The First Affiliated Hospital of Xi'an Jiaotong University School,Xi'an,Shaanxi,710061,China;Department of Hematology,The First Affiliated Hospital of Xi'an Jiaotong University School,Xi'an,Shaanxi,710061,China)

机构地区：[1]西安交通大学第一附属医院检验科,陕西西安710061 [2]西安交通大学第一附属医院血液内科,陕西西安710061

出　　处：《现代生物医学进展》2021年第22期4229-4233,4274,共6页Progress in Modern Biomedicine

基　　金：陕西省国际科技合作交流计划项目(2016KW-007)。

摘　　要：目的:研究miR-134-5p对多发性骨髓瘤(multiple myeloma,MM)化疗敏感性的影响及其可能的作用机制。方法:CCK-8法测定人多发性骨髓瘤细胞KM3及其耐硼替佐米(bortezomib,BTZ)细胞株KM3/BTZ对BTZ的化疗敏感性,RT-PCR法检测KM3和KM3/BTZ细胞株中miR-134-5p和p21活化激酶3(p21 activated kinase 3,PAK3)mRNA的表达,生物信息学软件分析miR-134-5p的靶基因,荧光素酶报告实验进行验证,CCK-8法检测分别抑制miR-134-5p和PAK3后KM3/BTZ的化疗敏感性,Western-blot法检测抑制miR-134-5p后KM3/BTZ细胞株中PAK3蛋白的表达。结果:KM3/BTZ细胞株对BTZ的化疗敏感性显著低于KM3细胞株(P<0.05)。MiR-134-5p在KM3细胞株的表达显著高于KM3/BTZ细胞株,而PAK3 mRNA在KM3细胞株的表达显著低于KM3/BTZ细胞株(P<0.05)。PAK3为miR-134-5p的靶基因。MiR-134-5p inhibitor组和PAK3 siRNA组KM3/BTZ细胞株的化疗敏感性显著低于对照组(P<0.05)。MiR-134-5p inhibitor组PAK3蛋白的相对表达显著高于对照组(P<0.05)。结论:MiR-134-5p可提高KM3/BTZ细胞株的化疗敏感性,其机制可能与抑制PAK3的表达有关。Objective:To investigate the effect of mi R-134-5 p on chemosensitivity in multiple myeloma(MM)cells and its potential mechanism.Methods:The chemosensitivity of KM3 and KM3/BTZ cells were detected by CCK-8 method,the expression of mi R-134-5 p and p21 activated kinase 3(PAK3)m RNA in KM3 and KM3/BTZ cells were detected by RT-PCR,bioinformatics prediction software was used to predict potential target gene to mi R-134-5 p,and luciferase report experiment was used to verified,the chemosensitivity of KM3 and KM3/BTZ cells after inhibiting mi R-134-5 p and PAK3 were detected by CCK-8 method,the expression of PAK3 protein in KM3/BTZ cell after inhibiting mi R-134-5 p were detected by western-blot.Results:The chemosensitivity of KM3/BTZ cell was lower than KM3 cell(P<0.05).The expression of mi R-134-5 p in KM3 cell was higher than KM3/BTZ,while PAK3 m RNA was lower(P<0.05).PAK3 was a target gene of mi R-134-5 p.The chemosensitivity of KM3/BTZ cell of mi R-134-5 p inhibitor group and PAK3 si RNA group were lower than control group(P<0.05).The expression of PAK3 protein in mi R-134-5 p inhibitor group was higher than control group(P<0.05).Conclusion:Mi R-134-5 p could increase the chemosensitivity of KM3/BTZ cell,the potential mechanism might be via inhibiting expression of PAK3.

关 键 词：多发性骨髓瘤 化疗敏感性 miR-134-5p p21活化激酶3 

分 类 号：R733.3[医药卫生—肿瘤] R730.53[医药卫生—临床医学]