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Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading cause of HCC. Previous studies have demonstrated that expression of the tumor inhibitor miR-340 is significantly downregulated in HCC tiss...

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Autores principales: Xiong, Qiushuang, Wu, Shaoshuai, Wang, Jingwen, Zeng, Xianhuang, Chen, Jianwen, Wei, Mingcong, Guan, Haotong, Fan, Chengpeng, Chen, Lang, Guo, Deyin, Sun, Guihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389182/
https://www.ncbi.nlm.nih.gov/pubmed/28413603
http://dx.doi.org/10.1186/s13578-017-0144-8
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author Xiong, Qiushuang
Wu, Shaoshuai
Wang, Jingwen
Zeng, Xianhuang
Chen, Jianwen
Wei, Mingcong
Guan, Haotong
Fan, Chengpeng
Chen, Lang
Guo, Deyin
Sun, Guihong
author_facet Xiong, Qiushuang
Wu, Shaoshuai
Wang, Jingwen
Zeng, Xianhuang
Chen, Jianwen
Wei, Mingcong
Guan, Haotong
Fan, Chengpeng
Chen, Lang
Guo, Deyin
Sun, Guihong
author_sort Xiong, Qiushuang
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading cause of HCC. Previous studies have demonstrated that expression of the tumor inhibitor miR-340 is significantly downregulated in HCC tissues compared with normal liver tissues. However, the precise biological role of miR-340-5p in HBV–HCC and its molecular mechanism of action remain unknown. RESULTS: Expression of miR-340-5p was downregulated in HBV-associated HCC liver tissue and HBV-infected cells, facilitating migration of liver cancer cells. Signal transducer and activator of transcription (STAT)3 was found to be a direct functional target of miR-340-5p. The regulation of STAT3 expression by miR-340-5p was assessed using qRT-PCR and western blotting, and the effects of exogenous miR-340-5p and STAT3 on the migration of HBV-infected cells were evaluated in vitro using Transwell(®) and wound-healing assays. The expression of E-cadherin and vimentin, associated with epithelial–mesenchymal transition, was also assessed using Western blotting after transfection of miR-340-5p mimics and/or STAT3 expression vectors. Overexpression of STAT3 resulted in rescue of HBV effects, decreased E-cadherin expression, increased vimentin expression, and ultimately, enhanced cell migration. Re-introduction of the STAT3 CDS led to marked reversal of the inhibition of cell migration in HBV-infected cells mediated by miR-340-5p. CONCLUSIONS: Hepatitis B virus promotes the migration of liver cancer cells by downregulating miR-340-5p expression to induce STAT3 overexpression. Our results show that STAT3 plays a key role in regulating cell migration in HBV–HCC involving miR-340-5p.
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spelling pubmed-53891822017-04-14 Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression Xiong, Qiushuang Wu, Shaoshuai Wang, Jingwen Zeng, Xianhuang Chen, Jianwen Wei, Mingcong Guan, Haotong Fan, Chengpeng Chen, Lang Guo, Deyin Sun, Guihong Cell Biosci Research BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading cause of HCC. Previous studies have demonstrated that expression of the tumor inhibitor miR-340 is significantly downregulated in HCC tissues compared with normal liver tissues. However, the precise biological role of miR-340-5p in HBV–HCC and its molecular mechanism of action remain unknown. RESULTS: Expression of miR-340-5p was downregulated in HBV-associated HCC liver tissue and HBV-infected cells, facilitating migration of liver cancer cells. Signal transducer and activator of transcription (STAT)3 was found to be a direct functional target of miR-340-5p. The regulation of STAT3 expression by miR-340-5p was assessed using qRT-PCR and western blotting, and the effects of exogenous miR-340-5p and STAT3 on the migration of HBV-infected cells were evaluated in vitro using Transwell(®) and wound-healing assays. The expression of E-cadherin and vimentin, associated with epithelial–mesenchymal transition, was also assessed using Western blotting after transfection of miR-340-5p mimics and/or STAT3 expression vectors. Overexpression of STAT3 resulted in rescue of HBV effects, decreased E-cadherin expression, increased vimentin expression, and ultimately, enhanced cell migration. Re-introduction of the STAT3 CDS led to marked reversal of the inhibition of cell migration in HBV-infected cells mediated by miR-340-5p. CONCLUSIONS: Hepatitis B virus promotes the migration of liver cancer cells by downregulating miR-340-5p expression to induce STAT3 overexpression. Our results show that STAT3 plays a key role in regulating cell migration in HBV–HCC involving miR-340-5p. BioMed Central 2017-04-12 /pmc/articles/PMC5389182/ /pubmed/28413603 http://dx.doi.org/10.1186/s13578-017-0144-8 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Xiong, Qiushuang
Wu, Shaoshuai
Wang, Jingwen
Zeng, Xianhuang
Chen, Jianwen
Wei, Mingcong
Guan, Haotong
Fan, Chengpeng
Chen, Lang
Guo, Deyin
Sun, Guihong
Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression
title Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression
title_full Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression
title_fullStr Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression
title_full_unstemmed Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression
title_short Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression
title_sort hepatitis b virus promotes cancer cell migration by downregulating mir-340-5p expression to induce stat3 overexpression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389182/
https://www.ncbi.nlm.nih.gov/pubmed/28413603
http://dx.doi.org/10.1186/s13578-017-0144-8
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