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

摘要: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 IC₅₀ 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 IC50 值显著低于对照组( P<0. 01) ,OPM2 / H19 组硼替佐米 IC₅₀ 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。

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

Abstract: 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 relievesMM 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 IC₅₀ 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 IC₅₀ 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.