PRMT7抑制前列腺癌细胞体外迁移和侵袭的研究  

PRMT7 suppresses migration and invasion of prostate cancer cells in vitro

作　　者：胡平 何燕燕 孙馨悦 王建军 陈平[1] HU Ping;HE Yanyan;SUN Xinyue;WANG Jianjun;CHEN Ping(School of Life Science and Technology,Tongji University,Shanghai 200092,China;Department of Pathology,Shanghai Tenth People s Hospital,School of Medicine,Tongji University,Shanghai 200072,China;Department of Obstetrics and Gynecology,Shanghai East Hospital,School of Medicine,Tongji University,Shanghai 200123,China)

机构地区：[1]同济大学生命科学与技术学院,上海200092 [2]同济大学附属第十人民医院病理科,上海200072 [3]同济大学附属东方医院妇产科,上海200123

出　　处：《同济大学学报（医学版）》2023年第2期166-172,共7页Journal of Tongji University(Medical Science)

基　　金：国家自然科学基金(81773009)。

摘　　要：目的 研究PRMT7对前列腺癌细胞迁移和侵袭的影响及机制探究。方法 使用R软件从TCGA和GTEx数据库中获得正常前列腺和前列腺癌组织中PRMT7的转录组数据。Western印迹法检测细胞中PRMT7的蛋白水平。通过细胞划痕实验、Transwell迁移实验和Transwell侵袭实验评估细胞的迁移和侵袭。使用转录组测序分析和无标记定量蛋白质测序分析评估转录物和蛋白质水平。使用siRNA技术敲低KISS1R的表达。结果 TCGA和GTEx数据库显示PRMT7在前列腺癌组织的表达低于正常前列腺组织。PRMT7在前列腺癌细胞系中表达低于正常前列腺上皮细胞。细胞划痕实验、Transwell迁移和Transwell侵袭实验结果表明,PRMT7抑制前列腺癌细胞LNCaP和PC3的迁移和侵袭。全基因组转录组、蛋白质组测序分析以及Western印迹法结果显示,转移抑制基因KISS1R在转录和翻译水平均被PRMT7上调,敲除KISS1R可拯救肿瘤抑制表型。结论 本研究揭示了PRMT7在前列腺癌细胞中的抗肿瘤作用,进一步证明了KISS1R是PRMT7调控肿瘤细胞迁移和侵袭的下游效应分子,PRMT7可能是临床治疗前列腺癌的有效靶点。Objective To investigate the effect and mechanism of PRMT7 on migration and invasion of prostate cancer cells.Methods Transcriptome data of PRMT7 in normal prostate and prostate cancer tissues were obtained from TCGA and GTEx databases using R software.The expression levels of PRMT7 protein in cells were detected by Western blot.Migration and invasion of PRMT7 cells were assessed using wound healing assay and Transwell assay.Transcripts and proteins levels were evaluated using transcriptome sequencing analysis and label-free quantitative protein sequencing analysis.KISS1R was knockdown by siRNA transfection.Results The expression of PRMT7 was lower in prostate cancer tissues than that in normal prostate tissues as analyzed in TCGA and GTEx datasets.The expression of PRMT7 was downregulated in prostate cancer cell lines LNCaP and PC3 and the overexpression of PRMT7 suppressed migration and invasion in the prostate cancer cells,as determined by wound healing assay,Transwell assays.The whole-genome transcriptome,proteome sequencing analysis and Western blotting showed that the metastasis suppressor gene KISS1R was up-regulated both at the transcriptional and translational level by upregulating PRMT7 expression.Knockdown of KISS1R reversed the tumor-suppressive phenotype.Conclusion The study demonstrates that PRMT7 plays an anti-oncogenic role in prostate cancer cells and KISS1R is a downstream effector molecule of PRMT7 in modulating tumor cell migration and invasion,suggesting that PRMT7 may be a potential target for the clinical treatment of prostate cancer.

关 键 词：前列腺癌 蛋白质精氨酸甲基转移酶7 迁移 侵袭 KiSS-1转移抑制受体 

分 类 号：R73[医药卫生—肿瘤]