Cargando…

Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop

Arsenic is a well-known of human carcinogen and miR-301a is an oncogenic microRNA, which links to oncogenesis, however, little is understood about its contribution to arsenic-induced cellular transformation and tumorigenesis. Here, we investigated the role of miR-301a during arsenic-induced cellular...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhong, Mingtian, Huang, Zhujuan, Wang, Lei, Lin, Zhanwen, Cao, Zhi, Li, Xun, Zhang, Fengxue, Wang, Hongqi, Li, Yong, Ma, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125593/
https://www.ncbi.nlm.nih.gov/pubmed/30185897
http://dx.doi.org/10.1038/s41598-018-31516-0
_version_ 1783353185662926848
author Zhong, Mingtian
Huang, Zhujuan
Wang, Lei
Lin, Zhanwen
Cao, Zhi
Li, Xun
Zhang, Fengxue
Wang, Hongqi
Li, Yong
Ma, Xiaodong
author_facet Zhong, Mingtian
Huang, Zhujuan
Wang, Lei
Lin, Zhanwen
Cao, Zhi
Li, Xun
Zhang, Fengxue
Wang, Hongqi
Li, Yong
Ma, Xiaodong
author_sort Zhong, Mingtian
collection PubMed
description Arsenic is a well-known of human carcinogen and miR-301a is an oncogenic microRNA, which links to oncogenesis, however, little is understood about its contribution to arsenic-induced cellular transformation and tumorigenesis. Here, we investigated the role of miR-301a during arsenic-induced cellular transformation and tumor formation. miR-301a was found to be upregulated during arsenic-induced BEAS-2B transformation and the overexpression of miR-301a was dependent on IL-6/STAT3 signaling. Inhibition of miR-301a leads to reduction of cell proliferation, colony formation and cell migration. By using dual luciferase assay, SMAD4 was confirmed to be a direct target of miR-301a in BEAS-2B cells and upregulation of SMAD4 is involved the restraining cell growth and migration. In addition, reducing of miR-301a expression enhances doxorubicin-induced cellular apoptosis of transformed BEAS-2B through up-regulating SMAD4. Furthermore, we demonstrated that downregulation of miR-301a in BEAS-2B attenuates tumor growth in the xenograft model by targeting SMAD4. Of note, the level of miR-301a expression correlated inversely with SMAD4 expression in clinical specimens of human lung cancer. Our findings ascertain that miR-301a is an oncogenic miRNA, which targets SMAD4 to establish an essential mechanism for arsenic-induced carcinogenesis, IL-6/STAT3/miR-301a/SMAD4 signaling pathways.
format Online
Article
Text
id pubmed-6125593
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-61255932018-09-10 Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop Zhong, Mingtian Huang, Zhujuan Wang, Lei Lin, Zhanwen Cao, Zhi Li, Xun Zhang, Fengxue Wang, Hongqi Li, Yong Ma, Xiaodong Sci Rep Article Arsenic is a well-known of human carcinogen and miR-301a is an oncogenic microRNA, which links to oncogenesis, however, little is understood about its contribution to arsenic-induced cellular transformation and tumorigenesis. Here, we investigated the role of miR-301a during arsenic-induced cellular transformation and tumor formation. miR-301a was found to be upregulated during arsenic-induced BEAS-2B transformation and the overexpression of miR-301a was dependent on IL-6/STAT3 signaling. Inhibition of miR-301a leads to reduction of cell proliferation, colony formation and cell migration. By using dual luciferase assay, SMAD4 was confirmed to be a direct target of miR-301a in BEAS-2B cells and upregulation of SMAD4 is involved the restraining cell growth and migration. In addition, reducing of miR-301a expression enhances doxorubicin-induced cellular apoptosis of transformed BEAS-2B through up-regulating SMAD4. Furthermore, we demonstrated that downregulation of miR-301a in BEAS-2B attenuates tumor growth in the xenograft model by targeting SMAD4. Of note, the level of miR-301a expression correlated inversely with SMAD4 expression in clinical specimens of human lung cancer. Our findings ascertain that miR-301a is an oncogenic miRNA, which targets SMAD4 to establish an essential mechanism for arsenic-induced carcinogenesis, IL-6/STAT3/miR-301a/SMAD4 signaling pathways. Nature Publishing Group UK 2018-09-05 /pmc/articles/PMC6125593/ /pubmed/30185897 http://dx.doi.org/10.1038/s41598-018-31516-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhong, Mingtian
Huang, Zhujuan
Wang, Lei
Lin, Zhanwen
Cao, Zhi
Li, Xun
Zhang, Fengxue
Wang, Hongqi
Li, Yong
Ma, Xiaodong
Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop
title Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop
title_full Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop
title_fullStr Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop
title_full_unstemmed Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop
title_short Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop
title_sort malignant transformation of human bronchial epithelial cells induced by arsenic through stat3/mir-301a/smad4 loop
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125593/
https://www.ncbi.nlm.nih.gov/pubmed/30185897
http://dx.doi.org/10.1038/s41598-018-31516-0
work_keys_str_mv AT zhongmingtian malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT huangzhujuan malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT wanglei malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT linzhanwen malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT caozhi malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT lixun malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT zhangfengxue malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT wanghongqi malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT liyong malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop
AT maxiaodong malignanttransformationofhumanbronchialepithelialcellsinducedbyarsenicthroughstat3mir301asmad4loop