脱氧核糖核酸酶1在肾细胞癌中的作用及机制研究  

The Mechanism of DNASE1L3 in Renal Cell Carcinoma

作　　者：曾艳[1] 祝恒成[1] 杨康 ZENG Yan;ZHU Hengcheng;YANG Kang(Department of Urology,Renmin Hospital of Wuhan University,Wuhan 443002,China)

机构地区：[1]武汉大学人民医院泌尿外科,武汉443002

出　　处：《生物技术进展》2024年第3期486-491,共6页Current Biotechnology

基　　金：国家自然科学基金项目(82100703)。

摘　　要：肾细胞癌(renal cell carcinoma,RCC)患者在手术后对放疗、化疗和靶向治疗均不敏感。前期研究证明,在肝癌中,脱氧核糖核酸酶1(deoxyribonuclease 1-like 3,DNASE1L3)可以分解包膜内的单链和双链DNA,通过弱化糖酵解的限速酶,抑制细胞周期、增殖和代谢。然而,DNASE1L3在肾癌中的作用和相关机制尚不清楚。从癌症基因组图谱数据库(the Cancer Genome Atlas,TCGA)中下载并分析了肾癌RNA测序数据;使用(Gene Expression Omnibus,GEO)数据库、人类蛋白质图谱数据库和免疫印迹验证DNASE1L3的表达水平;运用免疫相关数据库分析、划痕和侵袭实验,探究了DNASE1L3的作用和潜在机制。结果发现,在TCGA肾癌数据中,DNASE1L3表达量与患者的临床特征显著相关,且与患者生存期呈正相关;过表达DNASE1L3会抑制ACHN和786-O细胞的增殖和侵袭能力。结果表明,DNASE1L3可能成为肾癌患者诊断和治疗的潜在生物标志物。Renal cell carcinoma(RCC)patients are insensitive to radiotherapy,chemotherapy and targeted therapy after surgery.The previous study have proved that deoxyribonuclease 1-like 3(DNASE1L3)could decompose both membrane-encapsulated single and double-stranded DNA,and suppressed the cell cycle,proliferation and metabolism by weakening rate-limiting enzymes of glycolysis in hepatocellular carcinoma.However,the mechanism underlying the relationship between DNASE1L3 and the tumor immune microenvironment in renal cell carcinoma is still unclear.The RNA sequencing data of RCC were downloaded and analyzed from the Cancer Genome Atlas(TCGA)database.The expression levels of DNASE1L3 were verified using the Gene Expression Omnibus(GEO)database,Human Protein Atlas database and Western bloting.The role and potential mechanism of DNASE1L3 were investigated with immune-related database analysis,wound healing,and invasion.The results revealed that DNASE1L3 expression was significantly correlated with the clinical characteristics of patients and positively correlated with patient survival.In addition,DNASE1L3 overexpression inhibited the proliferation and invasion capacities of ACHN and 786-O cells.This study proved that DNASE1L3 may be a promising potential biomarker for the diagnosis and treatment of RCC patients.

关 键 词：脱氧核糖核酸酶1 肿瘤免疫 肾癌 免疫治疗 

分 类 号：Q291[生物学—细胞生物学] R736[医药卫生—肿瘤]