HIF-1α通过调控脂代谢关键基因促进肾癌细胞的侵袭
周建成;申骏龙;孙羿;程永毅;屈卫星
【期刊名称】《现代肿瘤医学》 【年(卷),期】2017(025)019
【摘要】目的:脂肪代谢在肾癌的发生、发展过程中至关重要.缺氧诱导因子-1α(HIF-1α)被认为是肾癌发生发展过程中关键的基因之一,其参与调控肾癌的侵袭转移过程.本研究探讨肾癌细胞侵袭过程中HIF-1α与脂肪代谢相关基因的关系.方法:采用免疫组织化学法检测人肾癌组织内HIF-1α、SCD1及FASN的表达,分析各基因之间的相关性.采用HIF-1 α过表达质粒或敲除shRNA沉默正常肾脏细胞HK-2及肾癌细胞ACHN内HIF-1α后,运用real-time PCR及Western blot技术检测脂肪代谢相关基因SCD1及FASN的表达改变情况.采用Transwell实验检测细胞体外侵袭能力,并运用SCD1及FASN的siRNA行基因沉默后,检测此两种基因对细胞侵袭能力的影响.结果:免疫组织化学结果显示SCD1及FASN在肾癌组织中的表达与HIF-1α呈显著正相关.HIF-1α过表达质粒能明显上调SCD1和FASN mRNA及蛋白的表达水平,反之,HIF-1α shRNA则明显抑制两种基因的表达.HIF-1α促进肾癌细胞ACHN的体外侵袭能力,而同时转染SCD1及FASN siRNA沉默基因表达后,细胞的侵袭能力减弱.结论:调控肾癌脂肪代谢的基因SCD1及FASN在HIF-1α所调控的肾癌细胞的侵袭过程中发挥重要作用.%Objective:Lipid-metabolism has been shown to play critical role in the development and progression of renal cell carcinoma (RCC).HIF-1 α is one of the essential genes which promote RCC invasion.The present study is aimed to investigate the potential
roles of lipid-metabolism related genes in HIF-1 α-regulated invasion of RCC cells.Methods:Immunohistochemistry was used to detect the expression of HIF-1 α,SCD1 and FASN in human RCC tissues,and Pearson correlation assay was used to analyze the associations between genes.HIF-1α over-expression plasmid and shRNA were transfected into normal kidney cell HK-2 and RCC cell ACHN,Western blot and real-time PCR were performed to detect the expression of two lipid-metabolism related genes SCD1 and FASN.Transwell assay was performed to detect the invasion abilities in vitro in ACHN cells introduced with HIF-1 α over expression plasmid,and when specific siRNAs targeting SCD1 and FASN were co-transfected into cells with HIF1 α over-expression plasmid,cell invasion was again determined.Results:Immunohistochemistry staining showed that the expression of SCD1 and FASN in human RCC tissues were positively correlated with HIF-1α.Over-expression of HIF-1 α significantly upregulated the mRNA and protein expression of SCD1 and FASN,whereas,HIF-1α shRNA decreased SCD1 and FASN expression.HIF-1α over-expression plasmid promoted ACHN invasion,but when SCD1 and FASN siRNAs were transfected into cells,the invasive ability of cells was ablated.Conclusion:Lipid-metabolism related genes SCD1 and FASN play crucial roles in HIF-1α regulated invasion of RCC cells. 【总页数】5页(3034-3038)
【关键词】肾癌;脂肪代谢;HIF-1α;侵袭;转移
【作者】周建成;申骏龙;孙羿;程永毅;屈卫星
【作者单位】陕西省人民医院泌尿外科,陕西西安710068;陕西省人民医院泌尿外科,陕西西安710068;延安大学医学院,陕西延安716000;陕西省人民医院泌尿外科,陕西西安710068;陕西省人民医院泌尿外科,陕西西安710068;陕西省人民医院泌尿外科,陕西西安710068 【正文语种】中文 【中图分类】R737.11 【文献来源】
https://www.zhangqiaokeyan.com/academic-journal-cn_journal-modern-oncology_thesis/0201236362358.html 【相关文献】
1.TRPM8调控EMT促进人肾癌细胞A498迁移及侵袭的作用研究 [J], 黄维; 陈洁仪; 黄俊勇; 周成宇
2.MACC1基因与肾癌转移的相关性及其对细胞侵袭能力的影响 [J], 尚超; 张辉; 宋永胜
3.miR-34a通过调控YY1抑制肾癌细胞的增殖及侵袭 [J], 王明丽; 李智; 徐晋豫; 翁文浩; 许闪闪
4.肿瘤酸性微环境促进肾癌细胞株769-P体外侵袭及其lncRNA表达谱分析 [J], 殷喜丰; 孙浩; 陈兵海
5.Cullin1基因在肾癌细胞增殖及迁移侵袭中的作用 [J], 王飞; 张磊; 陆勇; 谢广进; 白津; 郑骏年; 平季根
HIF-1α通过调控脂代谢关键基因促进肾癌细胞的侵袭
