>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
靶向抑制miR-21对多发性骨髓瘤细胞凋亡、增殖的影响及其作用机制的初步研究
作者:宋慧慧1 2  李原1  马钰1  凌孙凯歌1  葛峥1 2  黄培林1 
单位:1. 东南大学 医学院, 江苏 南京 210009;
2. 东南大学附属中大医院 血液内科, 江苏 南京 210009
关键词:多发性骨髓瘤 微小RNA-21 细胞株U266 PTEN FOXO1 
分类号:Q522;R730.23
出版年·卷·期(页码):2018·37·第五期(819-823)
摘要:

目的:研究miR-21对多发性骨髓瘤细胞增殖及凋亡产生的作用,初步探讨其作用机制。方法:qRT-PCR法检测miR-21在多发性骨髓瘤各细胞株中的表达水平。将miR-21抑制物及其阴性对照物转染至U266细胞株,RT-PCR法检测U266细胞miR-21的表达变化,CCK-8法检测miR-21对U266细胞增殖的影响,流式细胞术分析miR-21对U266细胞凋亡的作用,Western blotting检测U266细胞中PETN及FOXO1蛋白表达水平。结果:转染后实验组miR-21相对表达水平为0.286±0.031,低于阴性对照组(1.015±0.14)(P<0.05)。实验组U266细胞的增殖抑制率为(53.04±0.02)%,显著高于阴性对照组[(20.89±0.17)%](P<0.05);流式分析显示实验组U266细胞比阴性对照组凋亡明显增加[(28.53±3.23)%vs(5.12±0.63)%],差异具有统计学意义(P<0.05)。Western blotting结果显示,与阴性对照组、空白对照组相比,实验组U266细胞的PTEN、FOXO1蛋白表达水平均上调(P<0.05)。结论:靶向抑制miR-21可以促进多发性骨髓瘤细胞凋亡,抑制细胞增殖,这种作用可能是通过上调PTEN和FOXO1水平来实现的。

Objective:To explore the effect of miR-21 on proliferation and apoptosis of multiple myeloma cell lines and its molecular mechanism. Methods:miR-21 was detected on multiple myeloma (MM) cell lines by qRT-PCR. U266 cell line was transfected with miR-21 inhibitor and its negative control. qRT-PCR was used to detect the miR-21 expression changes. Cell proliferation and apoptosis were determined by using CCK-8 and flow cytometry. Western blotting was used to detect the protein expression of PTEN and FOXO1. Results:The relative expression of miR-21 in experimental group was 0.286±0.031 after transfection, which was lower than that in negative control group(P<0.05). The proliferation inhibition rate was (53.04±0.02)% in experimental group, which was down to (20.89±0.17)% in negative control group(P<0.05). The cellular apoptotic rate in the experimental group was significantly higher than that in the negative control group[(28.53±3.23)% vs(5.12±0.63)%](P<0.05). Western blotting analysis revealed up-regulation of PTEN and FOXO1 protein expression in experimental group by inhibiting miR-21 expression(P<0.05). Conclusion:Inhibiting miR-21 expression has distinct effects on apoptosis and proliferation inhibition, which is mediated by up-regulated levels of PTEN and FOXO1.

参考文献:

[1] JAHANGIR A,HOU J,HONG C.Role of micro-RNAs in drug resistance of multiple myeloma[J].Oncotarget,2016,37(7):60723-60735.
[2] ZHAO J J,CHU Z B,HU Y,et al.Targeting the miR-221-222/PUMA/BAK/BAX pathway abrogates dexamethasone resistance in multiple myeloma[J].Cancer Res,2015,75(20):4384-4397.
[3] MIRZAEI H R,SAHEBKAR A,MOHAMMADI M,et al.Circulating microRNAs in Hepatocellular Carcinoma:Potential Diagnostic and Prognostic Biomarkers[J].Curr Pharm Des,2016,22(34):5257-5269.
[4] SEKAR D,KRISHNAN R,THIRUGNANASAMBANTHAM K,et al.Significance of microRNA 21 in gastric cancer[J].Clin Res Hepatol Gastroenterol,2016,40(5):538-545.
[5] OKUGAWA Y,YAO L,TOIYAMA Y,et al.Prognostic impact of sarcopenia and its correlation with circulating miR-21 in colorectal cancer patients[J].Oncol Rep,2018,39(4):1555-1564.
[6] MUSILOVA K,MRAZ M.MicroRNAs in B-cell lymphomas:how a complex biology gets more complex[J].Leukemia,2015,29(5):1004-1017.
[7] LEI W,WANG S,YANG C,et al.Combined expression of miR-34a and Smac mediated by oncolytic vaccinia virus synergistically promote anti-tumor effects in Multiple Myeloma[J].Sci Rep,2016,6(8):32174.
[8] RANINGA P V,di TRAPANI G,VUCKOVIC S,et al.Targeted knockdown of DJ-1 induces multiple myeloma cell death via KLF6 upregulation[J].Apoptosis,2016,21(12):1422-1437.
[9] YVONNE T,LEV K,LEONARDO S,et al.Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs[J].Cell,2011,147(2):344-357.
[10] 黄海进,徐广峰,焦峰.hsa-miR-21的生物信息学特征分析[J].东南大学学报(医学版),2013,32(1):60-64.
[11] 王金行,丁奇,周雯雯,等.miR-21下调SPRY2表达对多发性骨髓瘤细胞增殖和侵袭能力的影响及其机制研究[J].现代肿瘤医学,2015,23(2):157-162.
[12] 孙利华,汪蕾.miRNA-21靶向调控子宫内膜癌PTEN基因MRE-21片段的研究[J].现代医学,2017,45(10):1442-1446.
[13] URBANEK P,KLOTA L O.Posttranscriptional regulation of FOXO expression:microRNAs and beyond[J].Br J Phamacol,2017,174(12):1514-1532.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 187076 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364