miR-22调节透明细胞肾细胞癌患者的侵袭、基因表达并预测总生存率

IF 1.1 Q4 ONCOLOGY Kidney Cancer Pub Date : 2019-05-07 DOI:10.3233/KCA-190051
Xue Gong, Hongjuan Zhao, M. Saar, D. Peehl, J. Brooks
{"title":"miR-22调节透明细胞肾细胞癌患者的侵袭、基因表达并预测总生存率","authors":"Xue Gong, Hongjuan Zhao, M. Saar, D. Peehl, J. Brooks","doi":"10.3233/KCA-190051","DOIUrl":null,"url":null,"abstract":"Background: Clear cell renal cell carcinoma (ccRCC) is molecularly diverse and distinct molecular subtypes show different clinical outcomes. MicroRNAs (miRNAs) are essential components of gene regulatory networks and play a crucial role in progression of many cancer types including ccRCC. Objective: Identify prognostic miRNAs and determine the role of miR-22 in ccRCC. Methods: Hierarchical clustering was done in R using gene expression profiles of over 450 ccRCC cases in The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis was performed to identify prognostic miRNAs in the TCGA dataset. RNA-Seq was performed to identify miR-22 target genes in primary ccRCC cells and Matrigel invasion assay was performed to assess the effects of miR-22 overexpression on cell invasion. Results: Hierarchical clustering analysis using 2,621 prognostic genes previously identified by our group demonstrated that ccRCC patients with longer overall survival expressed lower levels of genes promoting proliferation or immune responses, while better maintaining gene expression associated with cortical differentiation and cell adhesion. Targets of 26 miRNAs were significantly enriched in the 2,621 prognostic genes and these miRNAs were prognostic by themselves. MiR-22 was associated with poor overall survival in the TCGA dataset. Overexpression of miR-22 promoted invasion of primary ccRCC cells in vitro and modulated transcriptional programs implicated in cancer progression including DNA repair, cell proliferation and invasion. Conclusions: Our results suggest that ccRCCs with differential clinical outcomes have distinct transcriptomes for which miRNAs could serve as master regulators. MiR-22, as a master regulator, promotes ccRCC progression at least in part by enhancing cell invasion.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"3 1","pages":"119 - 132"},"PeriodicalIF":1.1000,"publicationDate":"2019-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190051","citationCount":"9","resultStr":"{\"title\":\"miR-22 Regulates Invasion, Gene Expression and Predicts Overall Survival in Patients with Clear Cell Renal Cell Carcinoma\",\"authors\":\"Xue Gong, Hongjuan Zhao, M. Saar, D. Peehl, J. Brooks\",\"doi\":\"10.3233/KCA-190051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Clear cell renal cell carcinoma (ccRCC) is molecularly diverse and distinct molecular subtypes show different clinical outcomes. MicroRNAs (miRNAs) are essential components of gene regulatory networks and play a crucial role in progression of many cancer types including ccRCC. Objective: Identify prognostic miRNAs and determine the role of miR-22 in ccRCC. Methods: Hierarchical clustering was done in R using gene expression profiles of over 450 ccRCC cases in The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis was performed to identify prognostic miRNAs in the TCGA dataset. RNA-Seq was performed to identify miR-22 target genes in primary ccRCC cells and Matrigel invasion assay was performed to assess the effects of miR-22 overexpression on cell invasion. Results: Hierarchical clustering analysis using 2,621 prognostic genes previously identified by our group demonstrated that ccRCC patients with longer overall survival expressed lower levels of genes promoting proliferation or immune responses, while better maintaining gene expression associated with cortical differentiation and cell adhesion. Targets of 26 miRNAs were significantly enriched in the 2,621 prognostic genes and these miRNAs were prognostic by themselves. MiR-22 was associated with poor overall survival in the TCGA dataset. Overexpression of miR-22 promoted invasion of primary ccRCC cells in vitro and modulated transcriptional programs implicated in cancer progression including DNA repair, cell proliferation and invasion. Conclusions: Our results suggest that ccRCCs with differential clinical outcomes have distinct transcriptomes for which miRNAs could serve as master regulators. MiR-22, as a master regulator, promotes ccRCC progression at least in part by enhancing cell invasion.\",\"PeriodicalId\":17823,\"journal\":{\"name\":\"Kidney Cancer\",\"volume\":\"3 1\",\"pages\":\"119 - 132\"},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2019-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.3233/KCA-190051\",\"citationCount\":\"9\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney Cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3233/KCA-190051\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney Cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3233/KCA-190051","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 9

摘要

背景:透明细胞肾细胞癌(ccRCC)具有分子多样性,不同的分子亚型表现出不同的临床结果。MicroRNAs (miRNAs)是基因调控网络的重要组成部分,在包括ccRCC在内的许多癌症类型的进展中起着至关重要的作用。目的:鉴定预后mirna并确定miR-22在ccRCC中的作用。方法:利用Cancer Genome Atlas (TCGA)中超过450例ccRCC病例的基因表达谱在R中进行分层聚类。采用Kaplan-Meier分析来鉴定TCGA数据集中的预后mirna。通过RNA-Seq鉴定原代ccRCC细胞中miR-22的靶基因,通过Matrigel侵袭实验评估miR-22过表达对细胞侵袭的影响。结果:我们小组先前鉴定的2621个预后基因的分层聚类分析表明,总生存期较长的ccRCC患者促进增殖或免疫反应的基因表达水平较低,同时更好地维持与皮质分化和细胞粘附相关的基因表达。2621个预后基因中有26个mirna的靶点显著富集,这些mirna本身具有预后作用。在TCGA数据集中,MiR-22与较差的总生存率相关。在体外,miR-22的过表达促进了原代ccRCC细胞的侵袭,并调节了涉及癌症进展的转录程序,包括DNA修复、细胞增殖和侵袭。结论:我们的研究结果表明,具有不同临床结果的ccrcc具有不同的转录组,mirna可以作为主要调控因子。MiR-22作为一种主调控因子,至少在一定程度上通过增强细胞侵袭来促进ccRCC的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
miR-22 Regulates Invasion, Gene Expression and Predicts Overall Survival in Patients with Clear Cell Renal Cell Carcinoma
Background: Clear cell renal cell carcinoma (ccRCC) is molecularly diverse and distinct molecular subtypes show different clinical outcomes. MicroRNAs (miRNAs) are essential components of gene regulatory networks and play a crucial role in progression of many cancer types including ccRCC. Objective: Identify prognostic miRNAs and determine the role of miR-22 in ccRCC. Methods: Hierarchical clustering was done in R using gene expression profiles of over 450 ccRCC cases in The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis was performed to identify prognostic miRNAs in the TCGA dataset. RNA-Seq was performed to identify miR-22 target genes in primary ccRCC cells and Matrigel invasion assay was performed to assess the effects of miR-22 overexpression on cell invasion. Results: Hierarchical clustering analysis using 2,621 prognostic genes previously identified by our group demonstrated that ccRCC patients with longer overall survival expressed lower levels of genes promoting proliferation or immune responses, while better maintaining gene expression associated with cortical differentiation and cell adhesion. Targets of 26 miRNAs were significantly enriched in the 2,621 prognostic genes and these miRNAs were prognostic by themselves. MiR-22 was associated with poor overall survival in the TCGA dataset. Overexpression of miR-22 promoted invasion of primary ccRCC cells in vitro and modulated transcriptional programs implicated in cancer progression including DNA repair, cell proliferation and invasion. Conclusions: Our results suggest that ccRCCs with differential clinical outcomes have distinct transcriptomes for which miRNAs could serve as master regulators. MiR-22, as a master regulator, promotes ccRCC progression at least in part by enhancing cell invasion.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Kidney Cancer
Kidney Cancer Multiple-
CiteScore
0.90
自引率
8.30%
发文量
23
期刊最新文献
Emerging Antibody-Drug Conjugate Therapies and Targets for Metastatic Renal Cell Carcinoma Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab Nephrotoxicity Associated with Contemporary Renal Cell Carcinoma Regimens: A Systematic Review and Meta-Analysis Targeted Literature Review of Outcomes to Initial Systemic Therapy for Advanced/Metastatic Non-Clear Cell Renal Cell Carcinoma in Observational Studies Fibrinogen Levels in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab: Results of a Multicenter Prospective Trial
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1