中国癌症杂志 ›› 2018, Vol. 28 ›› Issue (10): 740-748.doi: 10.19401/j.cnki.1007-3639.2018.10.004

• 论著 • 上一篇    下一篇

PSMD7基因在人食管鳞癌组织中的表达及影响癌细胞增殖、凋亡的机制研究

张进忠1,石 科1,2,郭 丹1,杨 亮1,闫秀明1   

  1. 1.河南医学高等专科学校生物化学教研室,河南 郑州 451191 ;
    2.郑州大学细胞生物研究室,河南 郑州450008
  • 出版日期:2018-10-30 发布日期:2018-11-12
  • 通信作者: 张进忠 E-mail: jinzhongzhang1@163.com
  • 基金资助:
    河南省高等学校重点科研项目(16A310008,18A310015);河南省科技攻关计划项目(152102310161,162102310047);河南省医学科技攻关计划项目(201601027)。

Expression of PSMD7 in human esophageal squamous cell carcinoma specimens and its effects on cell proliferation and apoptosis

ZHANG Jinzhong1, SHI Ke1, 2, GUO Dan1, YANG Liang1, YAN Xiuming1   

  1. 1. Biochemistry Teaching and Research Office of Henan Medical College, Zhengzhou 451191, Henan Province, China; 2. Laboratory for Cell Biology of Zhengzhou University, Zhengzhou 450008, Henan Province, China
  • Published:2018-10-30 Online:2018-11-12
  • Contact: ZHANG Jinzhong E-mail: jinzhongzhang1@163.com

摘要: 背景与目的:26S蛋白酶体非ATP酶调节亚基7(26S proteasome non-ATPase regulatory subunit 7,PSMD7)作为组成19S蛋白酶体盖子结构的核心成员是否参与肿瘤的发生、发展,以及具体的分子机制尚不清楚。本实验将研究PSMD7基因在人食管鳞癌组织中的表达,以及对癌细胞增殖及凋亡的影响。方法:采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)和蛋白质印迹法(Western blot)检测食管鳞癌及其癌旁正常组织标本中PSMD7的mRNA及蛋白表达情况。在人食管鳞癌细胞系TE-1中,用慢病毒介导的RNA干扰技术下调PSMD7的表达,观察细胞增殖及凋亡的变化,检测线粒体膜电位的变化、细胞质中Cyt C的表达以及凋亡相关因子的表达。结果:PSMD7基因的mRNA和蛋白在食管鳞癌组织中的表达显著高于癌旁正常组织(P<0.05),PSMD7蛋白的高表达与淋巴结转移阳性呈正相关(P<0.05)。抑制PSMD7蛋白的表达可使细胞的增殖能力降低(P<0.05),并促进细胞的凋亡(P<0.05),同时线粒体膜电位降低,促进Cyt C释放进入细胞质,激活caspase级联反应,说明抑制PSMD7的表达诱导细胞凋亡是通过线粒体信号通路进行的。结论:PSMD7在食管鳞癌中呈高表达,并通过线粒体依赖的方式促进TE-1细胞凋亡。

关键词: PSMD7, 食管鳞癌, 增殖, 凋亡, 线粒体

Abstract: Background and purpose: As a core member of 19S proteasome lid structure, whether 26S proteasome non-ATPase regulatory subunit 7 (PSMD7) is involved in the tumorigenesis and its molecular mechanism are unclear. The expression of PSMD7 in human esophageal squamous cell carcinoma specimens was investigated, and its effects on cell proliferation and apoptosis  were examined. Methods: The mRNA expression and protein level of PSMD7 were detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. PSMD7 was downregulated by lentivirus transfection in TE-1 cells. Cell proliferation and apoptosis were examined after PSMD7 inhibition. The mitochondrial membrane potential, expression of Cyt C and apoptosis- related proteins were investigated. Results: PSMD7 was highly expressed in human esophageal squamous cell carcinoma specimens at both mRNA and protein levels (P<0.05). The overexpression of PSMD7 was positively correlated with lymph node metastasis (P<0.05). The proliferation of TE-1 cells was decreased and the apoptosis was induced upon PSMD7 downregulation (P<0.05). The mitochondrial membrane potential was reduced whereas expression of cytosolic Cyt C was increased, followed by activation of caspase cascade reaction, suggesting PSMD7 downregulation induced apoptosis through the mitochondrial pathway. Conclusion: PSMD7 is highly expressed in human esophageal squamous cell carcinoma. Cell apoptosis induced by PSMD7 downregulation may be processed via mitochondria-dependent pathway.

Key words: PSMD7, Esophageal squamous cell carcinoma, Proliferation, Apoptosis, Mitochondria