【摘要】 目的组蛋白去甲基化酶JMJD1A在多种恶性肿瘤的发生和发展中发挥重要作用,本研究探讨其在宫颈癌中的作用。方法选取2010年1月至2013年1月湖北民族大学附属民大医院诊治的110例原发性宫颈癌患者的宫颈癌组织(n=110)及癌旁组织(n=110,距离肿瘤组织≥3cm)纳入本次研究。采用组织免疫化学方法检测宫颈癌组织及癌旁组织中JMJD1A的表达情况,并采用瞬时转染和RNAi的方法在人正常宫颈细胞系和宫颈癌细胞中过表达和敲除JMJD1A表达,采用Western blot检测MAPK信号通路重要分子表达情况。结果免疫组织化学及Western blot检测结果表明,在宫颈癌组织和细胞系中检测到JMJD1A表达上调,敲除宫颈癌细胞系JMJD1A表达后细胞增殖能力下降,细胞凋亡增加,与正常宫颈癌细胞系相比,JMJD1A敲除细胞系中长非编码RNA MALAT1转录下调,且MAPK通路的多个重要分子的磷酸化水平下降。统计学结果提示,JMJD1A表达上调与宫颈癌患者肿瘤侵袭(P=0.005)、淋巴结转移(P=0.037)及TNM分期(P=0.004)密切相关。比例风险回归模型单一和多重变量分析结果表明,JMJD1A表达是宫颈癌患者总生存期预后的独立因素(HR为3.497,95%CI为1.746～6.599,P=0.003)。结论本研究证实JMJD1A在宫颈癌组织中表达普遍上调,其过表达是宫颈癌患者总生存期预后不良的重要因素,敲除JMJD1A表达后宫颈癌细胞发生凋亡,提示该蛋白有作为宫颈癌治疗的新靶点。更多还原

【Abstract】 Objective Histone demethylase JMJD1 A plays an important role in the occurrence and development of a variety of malignant tumors, and this study investigated its role in cervical carcinoma. Methods 110 patients with primary cervical cancer, diagnosed and treated in Minda Hospital of Hubei Minzu University from January 2010 to January 2013, were selected. Cervical cancer tissues(n=110) and adjacent tissues(n=110, ≥3 cm away from tumor tissues) were collected. The expression of JMJD1 A in cervical cancer tissues and adjacent tissues was detected by histoimmunochemistry, and the expression of JMJD1 A was overexpressed and knocked out in human normal cervical cell lines and cervical cancer cells by transient transfection and RNAi, and the expression of important molecules in MAPK signaling pathway was detected by Western blot. Results Immunohistochemistry and Western blot test show that, JMJD1 A expression up-regulated in cervical cancer tissue and cell lines. Knockout of JMJD1 A expression inhibited the cervical carcinoma cell proliferation, increased apoptosis. Compared with the normal cervical cancer cell lines, JMJD1 A knockout cell line MALAT1 long noncoding RNA transcription, and phosphorylation of MAPK pathway of several important molecular levels drop. Statistical results suggested that the up-regulation of JMJD1 A expression was closely related to tumor invasion(P=0.005), lymph node metastasis(P=0.037) and TNM stage(P=0.004) in patients with cervical cancer. The single and multiple variables analysis of proportional hazard regression model showed that JMJD1 A expression was an independent factor for the prognosis of cervical cancer patients(HR 3.497, 95%CI 1.746～6.599, P=0.003). Conclusions This study confirmed that the expression of JMJD1 A was generally up-regulated in cervical cancer tissues, and its overexpression was an important factor for the poor prognosis of the overall survival of cervical cancer patients. The apoptosis of cervical cancer cells occurred after the knockout of JMJD1 A expression, suggesting that this protein could be a new target for the treatment of cervical cancer.更多还原