miR-22 Regulates Invasion, Gene Expression and Predicts Overall Survival in Patients with Clear Cell Renal Cell Carcinoma.
MicroRNA
TCGA
clear cell renal cell carcinoma
miR-22
survival
Journal
Kidney cancer (Clifton, Va.)
ISSN: 2468-4570
Titre abrégé: Kidney Cancer
Pays: United States
ID NLM: 101735372
Informations de publication
Date de publication:
07 Aug 2019
07 Aug 2019
Historique:
entrez:
26
11
2019
pubmed:
26
11
2019
medline:
26
11
2019
Statut:
epublish
Résumé
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. Identify prognostic miRNAs and determine the role of miR-22 in ccRCC. 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. 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 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
Identify prognostic miRNAs and determine the role of miR-22 in ccRCC.
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31763513
doi: 10.3233/KCA-190051
pii: KCA190051
pmc: PMC6839454
doi:
Types de publication
Journal Article
Langues
eng
Pagination
119-132Subventions
Organisme : NCI NIH HHS
ID : U01 CA152737
Pays : United States
Informations de copyright
© 2019 – IOS Press and the authors. All rights reserved.
Déclaration de conflit d'intérêts
The authors have no conflict of interest to report.
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