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中国癌症防治杂志

中国癌症防治杂志 ›› 2020, Vol. 12 ›› Issue (1): 21-27.doi: 10.3969/j.issn.1674-5671.2020.01.04

• 基础研究 • 上一篇    下一篇

MCUR1表达对卵巢癌细胞生长的影响及作用机制

  

  1. 河南大学药学院；空军军医大学唐都医院普外科；空军军医大学西京医院妇产科；延安大学医学院
  • 出版日期:2020-02-25 发布日期:2020-03-10

Effect of MCUR1 expression on the growth of ovarian cancer cells and its mechanism

  • Online:2020-02-25 Published:2020-03-10
  • Contact: 鲍登克 E-mail：bdkmydy12004@126.com

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摘要：  目的 探讨线粒体钙单向转运体调节分子1（mitochondrial calcium uniporter regulator 1，MCUR1）与卵巢癌患者预后的关系，及其对卵巢癌细胞增殖和凋亡的影响和可能的作用机制。方法 从TCGA（the cancer genome atlas）数据库下载372例卵巢癌患者数据集，采用Kaplan-Meier法分析MCUR1与卵巢癌患者预后的关系。采用免疫组织化学法检测MCUR1在卵巢癌组织中的表达水平。转染MCUR1干扰片段及过表达质粒至卵巢癌Ａ2780细胞（siMCUR1组和MCUR1组），分别设置相应阴性对照（siCtrl组和EV组）。采用qRT-PCR和Western blot实验检测转染效果。采用MTS法、克隆形成实验检测细胞增殖情况。裸鼠皮下荷瘤后采用免疫组织化学法和组织TUNEL法检测增殖和凋亡情况，Western blot检测细胞增殖和凋亡相关分子的表达情况。结果 MCUR1高表达组中位生存期高于低表达组（53.7 个月 vs 41.3 个月，P=0.003）。与siCtrl组相比，siMCUR1组细胞增殖能力升高（P<0.01），裸鼠皮下荷瘤生长速度加快（P<0.01），Ki67表达升高（P<0.01），细胞凋亡能力减弱（P<0.05），p53、Caspase-3和Bax蛋白表达下调，而Bcl2、Cyclin D1和Cyclin E蛋白表达上调；与EV组相比，MCUR1组细胞增殖能力下降（P<0.01），裸鼠皮下荷瘤生长速度减缓（P<0.01），Ki67表达降低（P<0.01），细胞凋亡能力增强（P<0.05），p53、Ｃaspase-3和Bax蛋白表达上调，而Bcl2、Cyclin D1和Cyclin E蛋白表达下调。结论 MCUR1通过调控p53通路进而调控卵巢癌细胞的增殖与凋亡，MCUR1可能作为抑癌因子在卵巢癌中发挥作用，有望成为卵巢癌诊断及治疗靶点。

关键词: 卵巢癌, 线粒体钙单向转运体调节因子1, 增殖, 凋亡, 预后

Abstract: Objective To investigate the relationship between mitochondrial calcium uniporter regulator 1（MCUR1） and the prognosis of ovarian cancer patients，and the effect of MCUR1 on the proliferation and apoptosis of ovarian cancer cells as well as its possible mechanism. Methods The data of 372 ovarian cancer patients were downloaded from the Cancer Genome Atlas （TCGA） database. The Kaplan-Meier method was used to analyze the relationship between MCUR1 and the prognosis of ovarian cancer patients. Immunohistochemistry was used to detect the expression of MCUR1 in ovarian cancer tissues. Ovarian cancer A2780 cells were transfected with MCUR1 interference fragments and overexpression plasmids（siMCUR1 group and MCUR1 group），and corresponding negative controls（siCtrl and EV group） were set respectively. qRT-PCR and Western blot assay were used to detect the effect of MCUR1 intervention. MTS method and clone formation experiment were used to detect cell proliferation. Immunohistochemical and TUNEL staining methods were used to detect proliferation and apoptosis after tumor-bearing subcutaneously in nude mice. The Western blot was used to detect proliferation and apoptosis-related molecules. Results The median overall survival of the MCUR1 high expression group was higher than that of the low expression group（53.7 months vs 41.3 months，P=0.003）. Compared with the siCtrl group，the cell proliferation ability of  the  si MCUR1 group increased（P<0.01），the growth of subcutaneous tumors in nude mice accelerated（P<0.01），Ki67 expression increased（P<0.01），and the apoptotic capacity decreased（P<0.05）； the expressions of p53，Caspase-3，and Bax protein decreased，whereas the expressions of Bcl2，Cyclin D1，and Cyclin E protein increased. Compared with the EV group，the cell proliferation ability of the MCUR1 group decreased（P<0.01），the growth of subcutaneous tumor-bearing tumors in nude mice slowed down（P<0.01），Ki67 expression decreased （P<0.01），and apoptotic capacity increased （P<0.05）； the expressions of p53，Caspase-3，and Bax proteins increased，whereas the expressions of Bcl2，Cyclin D1，and Cyclin E proteins increased. Conclusions MCUR1 regulates the proliferation and apoptosis of ovarian cancer cells by regulating the p53 pathway. MCUR1 may play a role as a tumor suppressor in ovarian cancer and become a target for diagnosis and treatment of ovarian cancer.

Key words: Ovarian cancer, MCUR1, Proliferation, Apoptosis, Prognosis

中图分类号: 

  • R737.31