长链非编码RNA NEAT1影响骨髓瘤细胞ATO敏感性的作用研究  

Study on the effect of long non-coding RNA NEAT1 on ATO sensitivity of myeloma cells

作　　者：潘韶英 朱斌[1] 王素丽 丁志勇[1] 赵文理[1] PAN Shao-ying;ZHU Bin;WANG Su-li;DING Zhi-yong;ZHAO Wen-li(Department of Hematology,South Branch of the Sixth People′s Hospital Affiliated to Shanghai Jiaotong University,Fengxian District Central Hospital,Shanghai 201499,China)

机构地区：[1]上海交通大学附属第六人民医院南院(上海市奉贤区中心医院)血液内科,上海201499

出　　处：《实用药物与临床》2022年第7期584-588,共5页Practical Pharmacy and Clinical Remedies

基　　金：上海市奉贤区科学技术发展基金(20171008)。

摘　　要：目的探讨长链非编码RNA NEAT1影响骨髓瘤细胞三氧化二砷(ATO)敏感性的作用。方法不同浓度ATO处理骨髓瘤细胞OPM2、U266、RPMI8226及KM3。利用小分子干扰技术对细胞进行特异性NEAT1敲减,并分为NEAT1敲减组及对照组。CCK-8检测细胞增殖活性,并计算ATO抑制率。实时荧光定量PCR检测NEAT1及相关信号通路表达,免疫印迹技术检测相关蛋白表达。流式细胞检测细胞凋亡率。结果ATO对各种骨髓瘤细胞抑制率有显著不同,药物敏感性顺序为OPM2>RPMI8226>U266>KM3。NEAT1在各细胞中的表达含量与其ATO敏感性有一定相关性,ATO处理可导致NEAT1表达下调。与对照组细胞相比,NEAT1敲减组KM3细胞ATO敏感性显著增加,凋亡细胞增加。分子机制研究表明,敲减组细胞Notch信号通路较对照组减低,同时Notch1上游调节因子ADAM10及PRKD2表达显著下调。结论ATO可通过NEAT1及Notch信号通路表达显著抑制骨髓瘤细胞体外生长并诱导其凋亡。本研究为ATO临床应用提供实验依据,并为增强其疗效提供精准分子靶点。Objective To investigate the effect of long non-coding RNA NEAT1 on ATO sensitivity of myeloma cells.Methods Different concentrations of ATO were used to treat myeloma cells(OPM2,U266,RPMI8226 and KM3).Small interfering technology was used to make specific knockdown of NEAT1,which were divided into NEAT1 knockdown group and control group.NEAT1 and related signal pathways were detected by real-time fluorescent quantitative PCR.CCK-8 detected the changes in cell proliferation activity and ATO inhibitor rate was calculated.The related protein expression was detected by western blot.Flow cytometry detected the changes in cell apoptosis.Results The inhibitory rate of ATO on various myeloma cells was significantly different,and the order of drug sensitivity was OPM2>RPMI8226>U266>KM3.The expression level of NEAT1 in each cell had a certain correlation with its ATO sensitivity,and ATO treatment could lead to down-regulation of NEAT1 expression.Compared with the control group,the ATO sensitivity of KM3 cells in the NEAT1 knockdown group was significantly increased,and the apoptotic cells increased.Molecular mechanism studies showed that Notch signaling pathway in the knockdown group was lower than that in the control group,and the expression of the upstream regulators of Notch1,ADAM10 and PRKD2 was significantly down-regulated.Conclusion ATO can significantly inhibit the growth of myeloma cells in vitro and induce their apoptosis through the expression of NEAT1 and Notch signaling pathways.This study provides experimental evidence for the clinical application of ATO and provides precise molecular targets for enhancing its efficacy.

关 键 词：多发性骨髓瘤 长链非编码RNA NEAT1 三氧化二砷 NOTCH信号通路 细胞增殖 细胞凋亡 

分 类 号：R733.3[医药卫生—肿瘤]