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Down‐regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway

Somatic copy number alterations (CNAs) are a genomic hallmark of cancers. Among them, the chromosome 17p13.1 deletions are recurrent in hepatocellular carcinoma (HCC). Here, utilizing an integrative omics analysis, we screened out a novel tumour suppressor gene within 17p13.1, myosin heavy chain 10...

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Autores principales: Jin, Qian, Cheng, Min, Xia, Xia, Han, Yuqing, Zhang, Jing, Cao, Pengbo, Zhou, Gangqiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650048/
https://www.ncbi.nlm.nih.gov/pubmed/34738311
http://dx.doi.org/10.1111/jcmm.17036
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author Jin, Qian
Cheng, Min
Xia, Xia
Han, Yuqing
Zhang, Jing
Cao, Pengbo
Zhou, Gangqiao
author_facet Jin, Qian
Cheng, Min
Xia, Xia
Han, Yuqing
Zhang, Jing
Cao, Pengbo
Zhou, Gangqiao
author_sort Jin, Qian
collection PubMed
description Somatic copy number alterations (CNAs) are a genomic hallmark of cancers. Among them, the chromosome 17p13.1 deletions are recurrent in hepatocellular carcinoma (HCC). Here, utilizing an integrative omics analysis, we screened out a novel tumour suppressor gene within 17p13.1, myosin heavy chain 10 (MYH10). We observed frequent deletions (~38%) and significant down‐regulation of MYH10 in primary HCC tissues. Deletion or decreased expression of MYH10 was a potential indicator of poor outcomes in HCC patients. Knockdown of MYH10 significantly promotes HCC cell migration and invasion in vitro, and overexpression of MYH10 exhibits opposite effects. Further, inhibition of MYH10 markedly potentiates HCC metastasis in vivo. We preliminarily elucidated the mechanism by which loss of MYH10 promotes HCC metastasis by facilitating EGFR pathway activation. In conclusion, our study suggests that MYH10, a candidate target gene for 17p13 deletion, acts as a tumour suppressor and may serve as a potential prognostic indicator for HCC patients.
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spelling pubmed-86500482021-12-20 Down‐regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway Jin, Qian Cheng, Min Xia, Xia Han, Yuqing Zhang, Jing Cao, Pengbo Zhou, Gangqiao J Cell Mol Med Original Articles Somatic copy number alterations (CNAs) are a genomic hallmark of cancers. Among them, the chromosome 17p13.1 deletions are recurrent in hepatocellular carcinoma (HCC). Here, utilizing an integrative omics analysis, we screened out a novel tumour suppressor gene within 17p13.1, myosin heavy chain 10 (MYH10). We observed frequent deletions (~38%) and significant down‐regulation of MYH10 in primary HCC tissues. Deletion or decreased expression of MYH10 was a potential indicator of poor outcomes in HCC patients. Knockdown of MYH10 significantly promotes HCC cell migration and invasion in vitro, and overexpression of MYH10 exhibits opposite effects. Further, inhibition of MYH10 markedly potentiates HCC metastasis in vivo. We preliminarily elucidated the mechanism by which loss of MYH10 promotes HCC metastasis by facilitating EGFR pathway activation. In conclusion, our study suggests that MYH10, a candidate target gene for 17p13 deletion, acts as a tumour suppressor and may serve as a potential prognostic indicator for HCC patients. John Wiley and Sons Inc. 2021-11-04 2021-12 /pmc/articles/PMC8650048/ /pubmed/34738311 http://dx.doi.org/10.1111/jcmm.17036 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Jin, Qian
Cheng, Min
Xia, Xia
Han, Yuqing
Zhang, Jing
Cao, Pengbo
Zhou, Gangqiao
Down‐regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway
title Down‐regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway
title_full Down‐regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway
title_fullStr Down‐regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway
title_full_unstemmed Down‐regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway
title_short Down‐regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway
title_sort down‐regulation of myh10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the egfr pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650048/
https://www.ncbi.nlm.nih.gov/pubmed/34738311
http://dx.doi.org/10.1111/jcmm.17036
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