HINT2 downregulation promotes colorectal carcinoma migration and metastasis
Histidine triad nucleotide-binding 2 (HINT2), a member of the histidine triad proteins family, sensitizes cells to apoptosis in hepatocellular carcinoma. Here, we showed that HINT2 expression is lower in primary colorectal cancer (CRC) and metastasis tissues than in normal colorectal tissues, and th...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355117/ https://www.ncbi.nlm.nih.gov/pubmed/28088787 http://dx.doi.org/10.18632/oncotarget.14587 |
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author | Li, Weihua Cai, Shaoxin Wang, Le Yang, Changshun Zhou, Biaohuan Wang, Huan |
author_facet | Li, Weihua Cai, Shaoxin Wang, Le Yang, Changshun Zhou, Biaohuan Wang, Huan |
author_sort | Li, Weihua |
collection | PubMed |
description | Histidine triad nucleotide-binding 2 (HINT2), a member of the histidine triad proteins family, sensitizes cells to apoptosis in hepatocellular carcinoma. Here, we showed that HINT2 expression is lower in primary colorectal cancer (CRC) and metastasis tissues than in normal colorectal tissues, and that HINT2 abundance is inversely correlated with CRC tumor stage. Treating CRC cells with 5-aza-2′-deoxycytidine, a demethylating agent, upregulated HINT2, suggesting HINT2 downregulation is caused by methylation of the gene promoter. HINT2 downregulation increased tumor migration and invasion in vitro, promoted CRC cell metastasis in vivo, and increased expression of epithelial-to-mesenchymal transition (EMT) markers. Furthermore, HINT2 downregulation depended on hypoxia inducible factor (HIF)-2α-mediated transcriptional activation of zinc finger E-box-binding homeobox 1 (ZEB1). These results suggest that HINT2 downregulation promotes HIF-2α expression, which induces EMT and enhances CRC cell migration and invasion. HINT2 may thus a useful clinical indicator of CRC progression and metastasis risk. |
format | Online Article Text |
id | pubmed-5355117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53551172017-04-15 HINT2 downregulation promotes colorectal carcinoma migration and metastasis Li, Weihua Cai, Shaoxin Wang, Le Yang, Changshun Zhou, Biaohuan Wang, Huan Oncotarget Research Paper Histidine triad nucleotide-binding 2 (HINT2), a member of the histidine triad proteins family, sensitizes cells to apoptosis in hepatocellular carcinoma. Here, we showed that HINT2 expression is lower in primary colorectal cancer (CRC) and metastasis tissues than in normal colorectal tissues, and that HINT2 abundance is inversely correlated with CRC tumor stage. Treating CRC cells with 5-aza-2′-deoxycytidine, a demethylating agent, upregulated HINT2, suggesting HINT2 downregulation is caused by methylation of the gene promoter. HINT2 downregulation increased tumor migration and invasion in vitro, promoted CRC cell metastasis in vivo, and increased expression of epithelial-to-mesenchymal transition (EMT) markers. Furthermore, HINT2 downregulation depended on hypoxia inducible factor (HIF)-2α-mediated transcriptional activation of zinc finger E-box-binding homeobox 1 (ZEB1). These results suggest that HINT2 downregulation promotes HIF-2α expression, which induces EMT and enhances CRC cell migration and invasion. HINT2 may thus a useful clinical indicator of CRC progression and metastasis risk. Impact Journals LLC 2017-01-10 /pmc/articles/PMC5355117/ /pubmed/28088787 http://dx.doi.org/10.18632/oncotarget.14587 Text en Copyright: © 2017 Li et al. http://creativecommons.org/licenses/by/3.0/ 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 credited. |
spellingShingle | Research Paper Li, Weihua Cai, Shaoxin Wang, Le Yang, Changshun Zhou, Biaohuan Wang, Huan HINT2 downregulation promotes colorectal carcinoma migration and metastasis |
title | HINT2 downregulation promotes colorectal carcinoma migration and metastasis |
title_full | HINT2 downregulation promotes colorectal carcinoma migration and metastasis |
title_fullStr | HINT2 downregulation promotes colorectal carcinoma migration and metastasis |
title_full_unstemmed | HINT2 downregulation promotes colorectal carcinoma migration and metastasis |
title_short | HINT2 downregulation promotes colorectal carcinoma migration and metastasis |
title_sort | hint2 downregulation promotes colorectal carcinoma migration and metastasis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355117/ https://www.ncbi.nlm.nih.gov/pubmed/28088787 http://dx.doi.org/10.18632/oncotarget.14587 |
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