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Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric Cancer

MicroRNAs (miRNAs) act as transcriptional regulators and play pivotal roles in carcinogenesis. According to miRNA target databases, one miRNA may regulate many genes as its targets, while one gene may be targeted by many miRNAs. These findings indicate that relationships between miRNAs and their tar...

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Autores principales: Hashimoto, Yutaka, Akiyama, Yoshimitsu, Yuasa, Yasuhito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648557/
https://www.ncbi.nlm.nih.gov/pubmed/23667495
http://dx.doi.org/10.1371/journal.pone.0062589
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author Hashimoto, Yutaka
Akiyama, Yoshimitsu
Yuasa, Yasuhito
author_facet Hashimoto, Yutaka
Akiyama, Yoshimitsu
Yuasa, Yasuhito
author_sort Hashimoto, Yutaka
collection PubMed
description MicroRNAs (miRNAs) act as transcriptional regulators and play pivotal roles in carcinogenesis. According to miRNA target databases, one miRNA may regulate many genes as its targets, while one gene may be targeted by many miRNAs. These findings indicate that relationships between miRNAs and their targets may not be one-to-one. However, many reports have described only a one-to-one, one-to-multiple or multiple-to-one relationship between miRNA and its target gene in human cancers. Thus, it is necessary to determine whether or not a combination of some miRNAs would regulate multiple targets and be involved in carcinogenesis. To find some groups of miRNAs that may synergistically regulate their targets in human gastric cancer (GC), we re-analyzed our previous miRNA expression array data and found that 50 miRNAs were up-regulated on treatment with 5-aza-2'-deoxycytidine in a GC cell line. The “TargetScan” miRNA target database predicted that some of these miRNAs have common target genes. We also referred to the GEO database for expression of these common target genes in human GCs, which might be related to gastric carcinogenesis. In this study, we analyzed two miRNA combinations, miR-224 and -452, and miR-181c and -340. Over-expression of both miRNA combinations dramatically down-regulated their target genes, DPYSL2 and KRAS, and KRAS and MECP2, respectively. These miRNA combinations synergistically decreased cell proliferation upon transfection. Furthermore, we revealed that these miRNAs were down-regulated through promoter hypermethylation in GC cells. Thus, it is likely that the relationships between miRNAs and their targets are not one-to-one but multiple-to-multiple in GCs, and that these complex relationships may be related to gastric carcinogenesis.
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spelling pubmed-36485572013-05-10 Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric Cancer Hashimoto, Yutaka Akiyama, Yoshimitsu Yuasa, Yasuhito PLoS One Research Article MicroRNAs (miRNAs) act as transcriptional regulators and play pivotal roles in carcinogenesis. According to miRNA target databases, one miRNA may regulate many genes as its targets, while one gene may be targeted by many miRNAs. These findings indicate that relationships between miRNAs and their targets may not be one-to-one. However, many reports have described only a one-to-one, one-to-multiple or multiple-to-one relationship between miRNA and its target gene in human cancers. Thus, it is necessary to determine whether or not a combination of some miRNAs would regulate multiple targets and be involved in carcinogenesis. To find some groups of miRNAs that may synergistically regulate their targets in human gastric cancer (GC), we re-analyzed our previous miRNA expression array data and found that 50 miRNAs were up-regulated on treatment with 5-aza-2'-deoxycytidine in a GC cell line. The “TargetScan” miRNA target database predicted that some of these miRNAs have common target genes. We also referred to the GEO database for expression of these common target genes in human GCs, which might be related to gastric carcinogenesis. In this study, we analyzed two miRNA combinations, miR-224 and -452, and miR-181c and -340. Over-expression of both miRNA combinations dramatically down-regulated their target genes, DPYSL2 and KRAS, and KRAS and MECP2, respectively. These miRNA combinations synergistically decreased cell proliferation upon transfection. Furthermore, we revealed that these miRNAs were down-regulated through promoter hypermethylation in GC cells. Thus, it is likely that the relationships between miRNAs and their targets are not one-to-one but multiple-to-multiple in GCs, and that these complex relationships may be related to gastric carcinogenesis. Public Library of Science 2013-05-08 /pmc/articles/PMC3648557/ /pubmed/23667495 http://dx.doi.org/10.1371/journal.pone.0062589 Text en © 2013 Hashimoto et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hashimoto, Yutaka
Akiyama, Yoshimitsu
Yuasa, Yasuhito
Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric Cancer
title Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric Cancer
title_full Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric Cancer
title_fullStr Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric Cancer
title_full_unstemmed Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric Cancer
title_short Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric Cancer
title_sort multiple-to-multiple relationships between micrornas and target genes in gastric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648557/
https://www.ncbi.nlm.nih.gov/pubmed/23667495
http://dx.doi.org/10.1371/journal.pone.0062589
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