网络出版日期: 2021-08-13
基金资助
国家自然科学基金(81571525);上海市教育委员会高峰高原学科建设计划(20161315)
Expression of protein arginine methyltransferase 5 in lung cancer and its mechanism of promoting lung cancer
Online published: 2021-08-13
Supported by
National Natural Science Foundation of China(81571525);Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20161315)
目的·探讨蛋白精氨酸甲基转移酶5（protein arginine methyltransferase 5，PRMT5）在肺癌中的表达及其对肺癌细胞增殖、迁移、侵袭能力的作用。方法·采用免疫组织化学法检测73对肺癌及癌旁组织中PRMT5的表达，并与患者的临床特征行相关性分析。在肺癌细胞NCI-H1299中下调PRMT5后，通过CCK8法和Transwell小室观察PRMT5对细胞增殖、迁移和侵袭功能的影响，并采用蛋白质印迹法检测上皮细胞-间充质转化相关蛋白（E钙黏蛋白、波形蛋白和转录因子SNAI1）的表达。利用公共数据库GEO（Gene Expression Omnibus，基因表达综合）和TCGA（The Cancer Genome Atlas，癌症基因组图谱）分别分析PRMT5在肿瘤细胞系、肺癌组织中的表达，并进一步分析组织中PRMT5表达和肺癌患者预后的关系。结果·免疫组织化学法检测结果显示，PRMT5在肺癌组织中的表达显著高于癌旁组织（P=0.000），且在肿瘤Ⅲ~Ⅳ期的表达高于Ⅰ~Ⅱ期（P=0.033）。下调PRMT5后，NCI-H1299细胞的增殖、迁移和侵袭能力下降，E钙黏蛋白表达增加、波形蛋白及转录因子SNAI1表达减少。TCGA数据库的肺癌测序数据显示PRMT5在肺癌组织中表达显著高于正常肺组织；且PRMT5高表达的肺腺癌患者总生存率较低（P=0.005），PRMT5高表达的肺鳞癌患者无复发生存率较低（P=0.028）。结论·PRMT5在肺癌组织中表达较高，可促进肺癌细胞的增殖、迁移和侵袭，PRMT5高表达和肺癌的不良预后有关。
关键词： 蛋白精氨酸甲基转移酶5; 肺癌; 增殖; 迁移; 上皮细胞-间充质转化
周冰倩 , 韩丽 , 陈哲逸 , 陈诗宇 , 郑英霞 . 蛋白精氨酸甲基转移酶5在肺癌中的表达及其促进肺癌的作用机制[J]. 上海交通大学学报（医学版）, 2021 , 41(8) : 1009 -1016 . DOI: 10.3969/j.issn.1674-8115.2021.08.003
·To investigate the expression of protein arginine methyltransferase 5 (PRMT5) in lung cancer and its effect on proliferation, migration and invasion of lung cancer cells.
· Immunohistochemistry was used to detect the expression of PRMT5 in 73 pairs of lung cancer tissues and adjacent tissues, and its correlation with clinical characteristics of patients was analyzed. After PRMT5 was down-regulated in lung cancer cell line NCI-H1299, the effects of PRMT5 on cell proliferation, migration and invasion were observed by CCK8 assay and Transwell chamber, and the expressions of E-cadherin, vimentin and transcription factor SNAI1 were detected by Western blotting. The expression of PRMT5 in tumor cell lines and lung cancer tissues was analyzed by using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database, respectively, and the relationship between the expression of PRMT5 in tissues and the prognosis of lung cancer patients was further analyzed.
·Immunohistochemistry showed that the expression of PRMT5 in lung cancer tissues was significantly higher than that in adjacent tissues (P=0.000), and the expression of PRMT5 in stage Ⅲ?Ⅳ was higher than that in stage Ⅰ?Ⅱ (P=0.033). After PRMT5 down-regulation, the proliferation, migration and invasion ability of NCI-H1299 cells decreased, the expression of E-cadherin increased and the expression of vimentin and SNAI1 decreased. The lung cancer sequencing data of TCGA database showed that the expression of PRMT5 in lung cancer tissues was significantly higher than that in normal lung tissues, and the lung adenocarcinoma patients and the lung squamous cell carcinoma patients with higher expression of PRMT5 had lower overall survival rate (P=0.005) and relapse-free survival rate (P=0.028), respectively.
· PRMT5 is highly expressed in lung cancer tissues, which can promote the proliferation, migration and invasion of lung cancer cells. High expression of PRMT5 is associated with poor prognosis of lung cancer.
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