基础医学与临床 ›› 2019, Vol. 39 ›› Issue (1): 47-52.

• 研究论文 • 上一篇    下一篇

MCUR1在多发性骨髓瘤中的作用

牟佼1,戴进前1,雷小茹1,宋艳萍1,徐莉2   

  1. 1. 西安市中心医院
    2. 空军军医大学第一附属医院血液科
  • 收稿日期:2018-01-24 修回日期:2018-05-30 出版日期:2019-01-05 发布日期:2018-12-28
  • 通讯作者: 徐莉 E-mail:18792782113@163.com
  • 基金资助:
    节律基因BMAL1与急性髓系白血病预后的相关性及分子机制研究;E2F1和EZH2双重调控自噬影响骨髓瘤细胞耐药的分子机制

Role of MCUR1 in multiple myeloma

  • Received:2018-01-24 Revised:2018-05-30 Online:2019-01-05 Published:2018-12-28

摘要: 目的 探讨MCUR1分子在多发性骨髓瘤(MM)患者中的表达变化,观察其对MM细胞周期、凋亡的作用,初步分析其内在分子机制。方法 设瞬时转染MCUR1干涉片段1和2的白血病RPMI 8226细胞作为实验组(命名为siMCUR1-1和siMCUR1-2细胞),阴性干涉片段转染的RPMI 8226细胞(命名为siCtrl细胞)作为对照组;实时定量PCR方法测定MCUR1在MM患者及正常对照者骨髓单个核细胞中的表达水平;实时定量PCR和Western blot方法检测MCUR1沉默效果;用CCK-8法和流式细胞计量术分别测定沉默MCUR1后细胞增殖、细胞周期和凋亡,Western blot检测MCUR1沉默后p53及其下游分子表达变化。结果 与对照者相比,MCUR1在MM患者中的表达显著升高(P<0.05);MM细胞系RPMI 8226中干扰MCUR1后,与对照组相比,细胞增殖显著减慢(P<0.05),G1期细胞比例增加,S期细胞比例减少,细胞凋亡比例增加;与对照组相比,干扰MCUR1组细胞内p53、BAX蛋白表达增加,BCL2、cyclin D1和cyclin E蛋白表达减少。结论 MCUR1在MM患者中表达上调,MCUR1通过抑制p53通路进而促进MM细胞增殖。

关键词: MCUR1, 细胞周期, 细胞凋亡, p53, 多发性骨髓瘤

Abstract: Objective To explore the expression of MCUR1 in MM patients, and to analyze the effect and molecular mechanism of MCUR1 on the cell cycle and apoptosis of MM cells lines. Methods The leukemia RPMI 8226 cells transiently transfected with the MCUR1 small interfering RNA1 and 2 were used as experimental groups (siMCUR1-1 and siMCUR1-2), and paralleled with negative control siRNA (siCtrl) as the control group. The mRNA expression of MCUR1 in MM patients and control group was analyzed by real-time PCR. The effect of silencing MCUR1 was detected by real-time PCR and Western blot. The effects of MCUR1 on the cell growth, cell cycle and apoptosis in RPMI 8226 cells were detected by using CCK-8 and flow cytometry respectively. Detection the protein expression of p53 and its downstream molecular by Western blot. Results Compared with normal group, the MCUR1 mRNA expression in MM patients was higher (P<0.05). Compared with the control group, the cell growth of the siMCUR1 groups were significantly decreased in RPMI 8226 cells (P<0.05), and the percentage of siMCUR1 cells in G1 phase was significantly increased,while the percentage of siMCUR1 cells in S phase was significantly decreased. The apoptosis percentage of siMCUR1 cells was higher than that in the control cells. The protein level of p53 and BAX in the siMCUR1 cells were higher than that in the control cells, while the protein level of BCL2, Cyclin D1 and Cyclin E in the siMCUR1 cells were lower than that in the control cells. Conclusions The expression of MCUR1 is raised in MM patients, while MCUR1 promotes MM cells growth through down-regulation of p53.

Key words: MCUR1, cell cycle, apoptosis, p53, multiple myeloma