Cargando…

Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells

The alterations of micro RNAs (miRNAs) and their potential roles in arsenite-induced tumorigenesis are still poorly understood. In this study, miRNA Array was used to detect the expression level of miRNAs in human bronchial epithelial (HBE) cells that were transformed by 2.5 μM arsenite for 13 weeks...

Descripción completa

Detalles Bibliográficos
Autores principales: Gu, Shiyan, Sun, Donglei, Li, Xinyang, Zhang, Zunzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664104/
https://www.ncbi.nlm.nih.gov/pubmed/28972549
http://dx.doi.org/10.3390/genes8100254
_version_ 1783274939469529088
author Gu, Shiyan
Sun, Donglei
Li, Xinyang
Zhang, Zunzhen
author_facet Gu, Shiyan
Sun, Donglei
Li, Xinyang
Zhang, Zunzhen
author_sort Gu, Shiyan
collection PubMed
description The alterations of micro RNAs (miRNAs) and their potential roles in arsenite-induced tumorigenesis are still poorly understood. In this study, miRNA Array was used to detect the expression level of miRNAs in human bronchial epithelial (HBE) cells that were transformed by 2.5 μM arsenite for 13 weeks. These cells exhibited a neoplastic phenotype manifested by increased levels of cellular proliferation and migration and clone formation. Subsequently, 191 dysregulated miRNAs were identified to be associated with arsenite-induced transformation by miRNA Array. Among them, six miRNAs were validated by their expression levels with quantitative real-time polymerase chain reaction (qPCR), and 17 miRNAs were further explored via their target genes as well as regulatory network. Three databases, TargetMiner, miRDB, and TarBase, were used to predict the target genes of the 17 miRNAs, and a total of 954 common genes were sorted. Results of Gene Ontology (GO) analyses showed that the 954 genes were involved in diverse terms of GO categories, such as positive regulation of macroautophagy, epithelial cell maturation, and synaptic vesicle clustering. Moreover, results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that most of these target genes were enriched in various cancer-related pathways, including non-small cell lung cancer, Wnt signaling pathway, cell cycle, and p53 signaling pathway. The miRNA-gene regulatory network, which was constructed by cytoscape software with miRNAs and their target genes, showed that miR-15b-5p, miR-106b-5p, and miR-320d were the core hubs. Collectively, our results provide new insights into miRNA-mediated mechanisms underlying arsenite-induced transformation, although more experimental verification is still needed to prove these predictions.
format Online
Article
Text
id pubmed-5664104
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-56641042017-11-06 Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells Gu, Shiyan Sun, Donglei Li, Xinyang Zhang, Zunzhen Genes (Basel) Article The alterations of micro RNAs (miRNAs) and their potential roles in arsenite-induced tumorigenesis are still poorly understood. In this study, miRNA Array was used to detect the expression level of miRNAs in human bronchial epithelial (HBE) cells that were transformed by 2.5 μM arsenite for 13 weeks. These cells exhibited a neoplastic phenotype manifested by increased levels of cellular proliferation and migration and clone formation. Subsequently, 191 dysregulated miRNAs were identified to be associated with arsenite-induced transformation by miRNA Array. Among them, six miRNAs were validated by their expression levels with quantitative real-time polymerase chain reaction (qPCR), and 17 miRNAs were further explored via their target genes as well as regulatory network. Three databases, TargetMiner, miRDB, and TarBase, were used to predict the target genes of the 17 miRNAs, and a total of 954 common genes were sorted. Results of Gene Ontology (GO) analyses showed that the 954 genes were involved in diverse terms of GO categories, such as positive regulation of macroautophagy, epithelial cell maturation, and synaptic vesicle clustering. Moreover, results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that most of these target genes were enriched in various cancer-related pathways, including non-small cell lung cancer, Wnt signaling pathway, cell cycle, and p53 signaling pathway. The miRNA-gene regulatory network, which was constructed by cytoscape software with miRNAs and their target genes, showed that miR-15b-5p, miR-106b-5p, and miR-320d were the core hubs. Collectively, our results provide new insights into miRNA-mediated mechanisms underlying arsenite-induced transformation, although more experimental verification is still needed to prove these predictions. MDPI 2017-10-03 /pmc/articles/PMC5664104/ /pubmed/28972549 http://dx.doi.org/10.3390/genes8100254 Text en © 2017 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
Gu, Shiyan
Sun, Donglei
Li, Xinyang
Zhang, Zunzhen
Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells
title Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells
title_full Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells
title_fullStr Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells
title_full_unstemmed Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells
title_short Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells
title_sort alterations of mirnas and their potential roles in arsenite-induced transformation of human bronchial epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664104/
https://www.ncbi.nlm.nih.gov/pubmed/28972549
http://dx.doi.org/10.3390/genes8100254
work_keys_str_mv AT gushiyan alterationsofmirnasandtheirpotentialrolesinarseniteinducedtransformationofhumanbronchialepithelialcells
AT sundonglei alterationsofmirnasandtheirpotentialrolesinarseniteinducedtransformationofhumanbronchialepithelialcells
AT lixinyang alterationsofmirnasandtheirpotentialrolesinarseniteinducedtransformationofhumanbronchialepithelialcells
AT zhangzunzhen alterationsofmirnasandtheirpotentialrolesinarseniteinducedtransformationofhumanbronchialepithelialcells