文章摘要
姜红云,邬 琳,葛俊丽,姚念玲,康 锋.miR-19通过Keap-Nrf2/HO-1信号通路对卵巢癌细胞增殖的影响[J].,2021,(17):3217-3221
miR-19通过Keap-Nrf2/HO-1信号通路对卵巢癌细胞增殖的影响
The Effect of miR-19 on the Proliferation of Ovarian Cancer Cells through the Keap-Nrf2/HO-1 Signaling Pathway
投稿时间:2021-02-05  修订日期:2021-02-28
DOI:10.13241/j.cnki.pmb.2021.17.004
中文关键词: miR-19  Keap-Nrf2/HO-1信号通路  卵巢癌  增殖
英文关键词: miR-19  Keap-Nrf2/HO-1 signaling pathway  Ovarian cancer  Proliferation
基金项目:陕西省卫生健康委科研基金项目(2018C007)
作者单位E-mail
姜红云 空军军医大学第一附属医院门诊部特需中心 陕西 西安 710000 jiang153194@163.com 
邬 琳 西电集团医院妇产科 陕西 西安710077  
葛俊丽 空军军医大学第一附属医院妇产科 陕西 西安 710000  
姚念玲 空军军医大学第一附属医院妇产科 陕西 西安 710000  
康 锋 陕西省渭南市妇幼保健院外科 陕西 渭南 714000  
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中文摘要:
      摘要 目的:研究卵巢癌组织和细胞中miR-19的表达,探讨其异常表达对卵巢癌细胞Kelch样环氧氯丙烷相关蛋白-1(Kelch-like epichlorohydrin-associated protein1,Keap1)--核因子E2相关因子2(nuclearfactor-E2-relatedfactor2,Nrf2) /血红素氧合酶-1(heme oxygenase1,HO-1)信号通路及卵巢癌细胞增殖的影响。方法:回顾性收集2019年1月至2020年12月于我院就诊的患者经病理切片诊断为卵巢癌上皮细胞的手术标本30例,卵巢良性肿瘤标本30例,正常卵巢组织标本30例。免疫组化检测不同标本中Keap1、Nrf2、HO-1的表达,检测卵巢组织及细胞中miR-19、Keap1、Nrf2、HO-1的mRNA表达水平,及卵巢癌细胞中Keap1、Nrf2、HO-1的蛋白表达水平。在OVCAR-3细胞中沉默miR-19后,Western Blot检测细胞内Keap1、Nrf2、HO-1蛋白表达水平,收集沉默miR-19,对照组,沉默Nrf2、对照组的OVCAR-3细胞,继续培养0 h、24 h、48 h后,检测细胞增殖和凋亡。结果:Keap1蛋白在卵巢癌组织中的阳性表达显著低于良性卵巢肿瘤组织及正常卵巢组织;Nrf2和HO-1蛋白在卵巢癌组织中的阳性表达显著低于良性卵巢肿瘤组织及正常卵巢组织(P<0.05);沉默miR-19抑制其表达后,细胞内Keap1 mRNA、蛋白表达水平明显升高,Nrf2、HO-1 mRNA表达水平无明显变化,蛋白表达水平明显降低(P<0.05);沉默miR-19 组、沉默Nrf2组与转染阴性对照组相比,增殖能力明显降低,凋亡能力明显升高(P<0.05)。结论:卵巢癌细胞中,miR-19表达水平升高,可通过调控Keap1-Nrf2/HO-1信号通路影响卵巢癌细胞的增值、凋亡能力。
英文摘要:
      ABSTRACT Objective: To investigate the expression of miR-19 in ovarian cancer tissues and cells, and to explore the effect of its abnormal expression on the Kelch like epichlorohydrin related protein-1(Keap1)-nuclear factor E2 related factor 2(Nrf2)/ heme oxygenase-1(HO-1) signaling pathway and proliferation of ovarian cancer cells. Methods: Retrospective collection 30 cases of ovarian cancer epithelial cells diagnosed by pathological section, 30 benign ovarian tumors, 30 normal ovarian tissue specimens From January 2019 to December 2020. The expression of Keap1, Nrf2, HO-1 in different specimens was detected by Immunohistochemical, the mRNA expression of miR-19, Keap1, Nrf2, HO-1 in ovarian tissue and cells was detected, the protein expression of Keap1, Nrf2, HO-1 in ovarian tissue and cells was detected. The protein expression of Keap1, Nrf2, HO-1 in OVCAR-3 cells of miR-19(-). Collect OVCAR-3 cells of miR-19 silence group, Control group, Nrf2-silence group, control group after incubating 0 h, 24 h, 48 h, MTT detects cell proliferation and apoptosis. Results: The positive expression of Keap1 protein in ovarian cancer tissue was significantly lower than that in benign ovarian tumor tissue and normal ovarian tissue, and the positive expression of Nrf2 and HO-1 protein in ovarian cancer tissue was significantly lower than that in benign ovarian tumor tissue and normal ovarian tissue (P<0.05). The expression level of Keap1 mRNA, protein in cells increased significantly after silencing miR-19, Nrf2, HO-1 mRNA expression level did not change significantly, and protein expression level decreased significantly(P<0.05). Compared with transfection negative control group, the proliferation ability and apoptosis ability of silencing miR-19 group and silencing Nrf2 group decreased significantly(P<0.05). Conclusion: miR-19 expression level in ovarian cancer cells is elevated, which can affect the value-added and apoptosis ability of ovarian cancer cells by regulating Keap1-Nrf2/HO-1 signaling pathway.
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