miR-21与多发性骨髓瘤患者预后的关系及其对化疗耐药的影响和机制  

Relationship between miR-21 and prognosis of patients with multiple myeloma and its effect and mechanism on chemotherapy resistance

作　　者：程灵灵 魏晓晶[2] 庄婧 刘莉莉 石林 任翠爱[4] CHENG Lingling;WEI Xiaojing;ZHUANG Jing;LIU Lili;SHI Lin;REN Cuiai(Graduate School of Weifang Medical University,Weifang 261000,China)

机构地区：[1]潍坊医学院研究生院,山东潍坊261000 [2]中国医学科学院北京协和医学院血液学研究所 [3]广西医科大学第一附属医院 [4]潍坊市人民医院

出　　处：《山东医药》2020年第2期14-17,共4页Shandong Medical Journal

基　　金：国家自然科学基金青年项目(81700209)

摘　　要：目的分析miR-21在多发性骨髓瘤(MM)中表达及与患者预后的关系,探讨其对化疗药物耐药性的影响和机制。方法选取36例MM患者、13例健康供者,磁珠分选骨髓组织中MM细胞,RT-qPCR法检测miR-21,分析其与MM患者预后的关系;将成功转染miR-21模拟物、miR-control质粒的人MM细胞ARP1分别命名为ARP1-OE细胞和ARP1-EV细胞,均加入化疗药物硼替佐米(5μmol/L)作用24、48、72 h,CCK8法测算细胞存活率以评价miR-21对MM细胞化疗耐药性的影响,蛋白印迹法检测硼替佐米作用48 h后细胞中c-Myc和Aurora A的表达水平。结果MM患者骨髓组织中MM细胞miR-21表达水高于健康供者(P<0.05),miR-21高表达的MM患者总生存期短于miR-21低表达者(P<0.05);在硼替佐米作用下,ARP1-OE细胞存活率均高于同时点的ARP1-EV细胞(P均<0.05);在硼替佐米作用48 h后,ARP1-OE细胞c-Myc和Aurora A表达水平高于ARP1-EV细胞(P均<0.05)。结论miR-21在MM患者的表达水平升高,miR-21高表达者总生存期缩短;miR-21过表达可降低MM细胞对硼替佐米的敏感性,该作用与其上调c-Myc和Aurora A表达有关。Objective To observe the expression of miR-21 in multiple myeloma(MM)and its relationship with the prognosis of patients,and to investigate its influence and mechanism on chemotherapy drug resistance.Methods Thirty-six MM patients and thirteen healthy donors were selected.Magnetic beads were used to separate MM cells from bone marrow.RT-qPCR was used to detected the expression of miR-21.The relationship between miR-21 and the prognosis of MM patients was analyzed.ARP1 cells transfected with miR-21 mimics and mir-control plasmids were named ARP1-OE and ARP1-EV,respectively.The chemotherapeutic drug bortezomib(5μmol/L)was added for 24,48 and 72 h.CCK-8 was used to measure the cell survival rate and evaluate the impact of miR-21 on the resistance of MM.The expression levels of c-Myc and Aurora A in the cells after 48 hours of bortezomib treatment were detected by Western blotting.Results The expression of miR-21 in the bone marrow tissues of MM patients was higher than that of healthy donors(P<0.05),and the overall survival time(OS)of MM patients with high expression of miR-21 was shorter than that of those with low expression of miR-21(P<0.05).Under the action of bortezomib,the survival rate of ARP1-OE cells was higher than that of ARP1-EV cells at the same time point(P<0.05).After 48-hour bortezomib treatment,the expression levels of c-Myc and Aurora A in ARP1-OE cells were higher than those in the ARP1-EV cells(both P<0.05).Conclusions The expression level of miR-21 increases in MM patients,and the OS of patients with high expression of miR-21 is significantly shortened.MiR-21 over-expression can reduce the sensitivity of MM cells to bortezomib,which is related to the up-regulation of c-myc and Aurora A expression.

关 键 词：MIR-21 多发性骨髓瘤 预后 化疗耐药 C-MYC蛋白 AURORA A蛋白 

分 类 号：R733.3[医药卫生—肿瘤]