Cargando…
A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma
MicroRNAs are ~22 nucleotide RNAs that regulate gene expression at the post-transcriptional level by binding messenger RNA transcripts. miR-21 is described as an oncomiR whose steady-state levels are commonly increased in many malignancies, including hepatocellular carcinoma (HCC). Methods known as...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877712/ https://www.ncbi.nlm.nih.gov/pubmed/29538313 http://dx.doi.org/10.3390/ijms19030851 |
_version_ | 1783310755801595904 |
---|---|
author | Koenig, Aaron Balasingam Barajas, Juan Martín Guerrero, María Jose Ghoshal, Kalpana |
author_facet | Koenig, Aaron Balasingam Barajas, Juan Martín Guerrero, María Jose Ghoshal, Kalpana |
author_sort | Koenig, Aaron Balasingam |
collection | PubMed |
description | MicroRNAs are ~22 nucleotide RNAs that regulate gene expression at the post-transcriptional level by binding messenger RNA transcripts. miR-21 is described as an oncomiR whose steady-state levels are commonly increased in many malignancies, including hepatocellular carcinoma (HCC). Methods known as cross-linking and immunoprecipitation of RNA followed by sequencing (CLIP-seq) have enabled transcriptome-wide identification of miRNA interactomes. In our study, we use a publicly available Argonaute-CLIP dataset (GSE97061), which contains nine HCC cases with matched benign livers, to characterize the miR-21 interactome in HCC. Argonaute-CLIP identified 580 miR-21 bound target sites on coding transcripts, of which 332 were located in the coding sequences, 214 in the 3′-untranslated region, and 34 in the 5′-untranslated region, introns, or downstream sequences. We compared the expression of miR-21 targets in 377 patients with liver cancer from the data generated by The Cancer Genome Atlas (TCGA) and found that mRNA levels of 402 miR-21 targets are altered in HCC. Expression of three novel predicted miR-21 targets (CAMSAP1, DDX1 and MARCKSL1) correlated with HCC patient survival. Analysis of RNA-seq data from SK-Hep1 cells treated with a miR-21 antisense oligonucleotide (GSE65892) identified RMND5A, an E3 ubiquitin ligase, as a strong miR-21 candidate target. Collectively, our analysis identified novel miR-21 targets that are likely to play a causal role in hepatocarcinogenesis. |
format | Online Article Text |
id | pubmed-5877712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58777122018-04-09 A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma Koenig, Aaron Balasingam Barajas, Juan Martín Guerrero, María Jose Ghoshal, Kalpana Int J Mol Sci Article MicroRNAs are ~22 nucleotide RNAs that regulate gene expression at the post-transcriptional level by binding messenger RNA transcripts. miR-21 is described as an oncomiR whose steady-state levels are commonly increased in many malignancies, including hepatocellular carcinoma (HCC). Methods known as cross-linking and immunoprecipitation of RNA followed by sequencing (CLIP-seq) have enabled transcriptome-wide identification of miRNA interactomes. In our study, we use a publicly available Argonaute-CLIP dataset (GSE97061), which contains nine HCC cases with matched benign livers, to characterize the miR-21 interactome in HCC. Argonaute-CLIP identified 580 miR-21 bound target sites on coding transcripts, of which 332 were located in the coding sequences, 214 in the 3′-untranslated region, and 34 in the 5′-untranslated region, introns, or downstream sequences. We compared the expression of miR-21 targets in 377 patients with liver cancer from the data generated by The Cancer Genome Atlas (TCGA) and found that mRNA levels of 402 miR-21 targets are altered in HCC. Expression of three novel predicted miR-21 targets (CAMSAP1, DDX1 and MARCKSL1) correlated with HCC patient survival. Analysis of RNA-seq data from SK-Hep1 cells treated with a miR-21 antisense oligonucleotide (GSE65892) identified RMND5A, an E3 ubiquitin ligase, as a strong miR-21 candidate target. Collectively, our analysis identified novel miR-21 targets that are likely to play a causal role in hepatocarcinogenesis. MDPI 2018-03-14 /pmc/articles/PMC5877712/ /pubmed/29538313 http://dx.doi.org/10.3390/ijms19030851 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Koenig, Aaron Balasingam Barajas, Juan Martín Guerrero, María Jose Ghoshal, Kalpana A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma |
title | A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma |
title_full | A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma |
title_fullStr | A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma |
title_full_unstemmed | A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma |
title_short | A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma |
title_sort | comprehensive analysis of argonaute-clip data identifies novel, conserved and species-specific targets of mir-21 in human liver and hepatocellular carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877712/ https://www.ncbi.nlm.nih.gov/pubmed/29538313 http://dx.doi.org/10.3390/ijms19030851 |
work_keys_str_mv | AT koenigaaronbalasingam acomprehensiveanalysisofargonauteclipdataidentifiesnovelconservedandspeciesspecifictargetsofmir21inhumanliverandhepatocellularcarcinoma AT barajasjuanmartin acomprehensiveanalysisofargonauteclipdataidentifiesnovelconservedandspeciesspecifictargetsofmir21inhumanliverandhepatocellularcarcinoma AT guerreromariajose acomprehensiveanalysisofargonauteclipdataidentifiesnovelconservedandspeciesspecifictargetsofmir21inhumanliverandhepatocellularcarcinoma AT ghoshalkalpana acomprehensiveanalysisofargonauteclipdataidentifiesnovelconservedandspeciesspecifictargetsofmir21inhumanliverandhepatocellularcarcinoma AT koenigaaronbalasingam comprehensiveanalysisofargonauteclipdataidentifiesnovelconservedandspeciesspecifictargetsofmir21inhumanliverandhepatocellularcarcinoma AT barajasjuanmartin comprehensiveanalysisofargonauteclipdataidentifiesnovelconservedandspeciesspecifictargetsofmir21inhumanliverandhepatocellularcarcinoma AT guerreromariajose comprehensiveanalysisofargonauteclipdataidentifiesnovelconservedandspeciesspecifictargetsofmir21inhumanliverandhepatocellularcarcinoma AT ghoshalkalpana comprehensiveanalysisofargonauteclipdataidentifiesnovelconservedandspeciesspecifictargetsofmir21inhumanliverandhepatocellularcarcinoma |