长链非编码RNA H19在多发性骨髓瘤硼替佐米耐药中的作用研究

The Role of Long-chain Non-coding RNA H19 in Bortezomib-resisted Multiple Myeloma

目的探讨长链非编码RNA H19(lncRNA H19)在多发性骨髓瘤(multiple myeloma,MM)硼替佐米耐药中的作用。方法选取我院2017年2月―2018年12月治疗的初诊MM患者26例、硼替佐米化疗缓解MM患者25例及硼替佐米化疗后耐药复发MM患者22例。siRNA-H19和慢病毒转染人多发性骨髓瘤OPM2细胞。荧光定量Real-time PCR检测lncRNA H19表达。CCK-8细胞活力检测OPM2细胞对硼替佐米敏感性。结果对照组、初诊MM组、缓解MM组和耐药MM组lncRNA H19的2^(-△△Ct)值分别为(0.107±0.032)、(0.324±0.067)、(0.218±0.042)和(0.486±0.095),各组间具有显著性差异(P<0.01)。其中,初诊MM组显著高于对照组和缓解MM组(P<0.01),耐药MM组又显著高于初诊MM组(P<0.01)。对照组、OPM2/si-H19组、OPM2/NC组、OPM2/H19组和OPM2/Blank组细胞的IC_(50)值分别为(17.86±1.64)nmol/L、(6.83±1.05)nmol/L、(18.04±1.72)nmol/L、(31.14±3.57)nmol/L和(17.75±1.68)nmol/L。其中,对照组、OPM2/NC组和OPM2/Blank组无显著性差异(P>0.05),OPM2/si-H19组硼替佐米IC_(50)值显著低于对照组(P<0.01),OPM2/H19组硼替佐米IC_(50)值显著高于对照组(P<0.01)。结论MM患者lncRNA H19显著升高,高表达lncRNA H19可能参与了硼替佐米耐药过程。

Objective To explore the role of long-chain non-coding RNA H19(lncRNA H19)in bortezomibresisted multiple myeloma(MM).Method Twenty six newly diagnosed MM patients,25 chemotherapy relieves MM patients,and 22 bortezomib-resisted MM patients were selected.The human multiple myeloma OPM2 cells were transfected by siRNA-H19 and lentivirus.lncRNA H19 was detected by Real-time PCR analysis.The sensitivity of OPM2 cells to bortezomib was detected by CCK-8 cell viability analysis.Result The 2^(-△△Ct)values of lncRNA H19 in the control group,the newly diagnosed MM group,the remission MM group and the drug-resistant MM group were(0.107±0.032),(0.324±0.067),(0.218±0.042),and(0.486±0.095),respectively.There were significant differences among these groups(P<0.01).Which was significantly higher in MM patients than those in the control group(P<0.01),in the newly diagnosed MM patients than those in the remission MM patients(P<0.01),and in the drug-resistant MM patients than those in the newly diagnosed MM patients(P<0.01).The IC_(50) values of bortezomib to the control group,the OPM2/si-H19 group,the OPM2/NC group,the OPM2/H19 group and the OPM2/Blank group were(17.86±1.64)nmol/L,(6.83±1.05)nmol/L,(18.04±1.72)nmol/L,(31.14±3.57)nmol/L and(17.75±1.68)nmol/L,respectively.There were no significant differences among the control group,the OPM2/NC group,and the OPM2/Blank group(P>0.05).The IC_(50) values were lower in the OPM2/si-H19 group than that in the control group,and in the control group than that in the OPM2/H19 group(P<0.01).Conclusion High expression of lncRNA H19 may be involved in bortezomib resistance.