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TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: TMEM106A is involved in invasion and metastasis of HCC
Expression of transmembrane protein 106A (TMEM106A) has been reported to be dysregulated in several types of cancers. However, the role of TMEM106A in hepatocellular carcinoma (HCC) is still unknown. In the present study, we demonstrate that TMEM106A is markedly downregulated in HCC compared with no...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827947/ https://www.ncbi.nlm.nih.gov/pubmed/35713314 http://dx.doi.org/10.3724/abbs.2022069 |
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author | Shi, Shiming Wang, Biao Wan, Jinglei Song, Lina Zhu, Guiqi Du, Junxian Ye, Luxi Zhao, Qianqian Cai, Jialiang Chen, Qing Xiao, Kun He, Jian Yu, Lei Dai, Zhi |
author_facet | Shi, Shiming Wang, Biao Wan, Jinglei Song, Lina Zhu, Guiqi Du, Junxian Ye, Luxi Zhao, Qianqian Cai, Jialiang Chen, Qing Xiao, Kun He, Jian Yu, Lei Dai, Zhi |
author_sort | Shi, Shiming |
collection | PubMed |
description | Expression of transmembrane protein 106A (TMEM106A) has been reported to be dysregulated in several types of cancers. However, the role of TMEM106A in hepatocellular carcinoma (HCC) is still unknown. In the present study, we demonstrate that TMEM106A is markedly downregulated in HCC compared with normal liver tissue. In particular, tumor-specific DNA methylation of TMEM106A is frequently observed in tumor tissues from HCC patients. Immunohistochemistry and pyrosequencing reveal a significant relationship between TMEM106A methylation and downregulation of protein expression. Receiver operating characteristic (ROC) curve analysis reveals that methylation of TMEM106A in tumor samples is different from that in non-malignant adjacent tissues of HCC patients. Moreover, HCC patients with TMEM106A hypermethylation have a poor clinical prognosis. 5-Aza-2′-deoxycytidin treatment of hypermethylated TMEM106A in highly metastatic HCC cells increases the expression of TMEM106A. Functional assays reveal that overexpression of TMEM106A significantly suppresses the malignant behavior of HCC cells in vitro and decreases tumorigenicity and lung metastasis in vivo. Mechanistically, TMEM106A inhibits epithelial mesenchymal transition (EMT) of HCC cells through inactivation of the Erk1/2/Slug signaling pathway. In conclusion, our findings demonstrate that TMEM106A is an inhibitor of HCC EMT and metastasis, and TMEM106A is often transcriptionally downregulated by promoter methylation, which results in reduced levels of TMEM106A protein and predicts poor survival outcomes for HCC patients. |
format | Online Article Text |
id | pubmed-9827947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-98279472023-02-10 TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: TMEM106A is involved in invasion and metastasis of HCC Shi, Shiming Wang, Biao Wan, Jinglei Song, Lina Zhu, Guiqi Du, Junxian Ye, Luxi Zhao, Qianqian Cai, Jialiang Chen, Qing Xiao, Kun He, Jian Yu, Lei Dai, Zhi Acta Biochim Biophys Sin (Shanghai) Research Article Expression of transmembrane protein 106A (TMEM106A) has been reported to be dysregulated in several types of cancers. However, the role of TMEM106A in hepatocellular carcinoma (HCC) is still unknown. In the present study, we demonstrate that TMEM106A is markedly downregulated in HCC compared with normal liver tissue. In particular, tumor-specific DNA methylation of TMEM106A is frequently observed in tumor tissues from HCC patients. Immunohistochemistry and pyrosequencing reveal a significant relationship between TMEM106A methylation and downregulation of protein expression. Receiver operating characteristic (ROC) curve analysis reveals that methylation of TMEM106A in tumor samples is different from that in non-malignant adjacent tissues of HCC patients. Moreover, HCC patients with TMEM106A hypermethylation have a poor clinical prognosis. 5-Aza-2′-deoxycytidin treatment of hypermethylated TMEM106A in highly metastatic HCC cells increases the expression of TMEM106A. Functional assays reveal that overexpression of TMEM106A significantly suppresses the malignant behavior of HCC cells in vitro and decreases tumorigenicity and lung metastasis in vivo. Mechanistically, TMEM106A inhibits epithelial mesenchymal transition (EMT) of HCC cells through inactivation of the Erk1/2/Slug signaling pathway. In conclusion, our findings demonstrate that TMEM106A is an inhibitor of HCC EMT and metastasis, and TMEM106A is often transcriptionally downregulated by promoter methylation, which results in reduced levels of TMEM106A protein and predicts poor survival outcomes for HCC patients. Oxford University Press 2022-06-09 /pmc/articles/PMC9827947/ /pubmed/35713314 http://dx.doi.org/10.3724/abbs.2022069 Text en © The Author(s) 2021. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Shi, Shiming Wang, Biao Wan, Jinglei Song, Lina Zhu, Guiqi Du, Junxian Ye, Luxi Zhao, Qianqian Cai, Jialiang Chen, Qing Xiao, Kun He, Jian Yu, Lei Dai, Zhi TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: TMEM106A is involved in invasion and metastasis of HCC |
title | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: TMEM106A is involved in invasion and metastasis of HCC |
title_full | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: TMEM106A is involved in invasion and metastasis of HCC |
title_fullStr | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: TMEM106A is involved in invasion and metastasis of HCC |
title_full_unstemmed | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: TMEM106A is involved in invasion and metastasis of HCC |
title_short | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: TMEM106A is involved in invasion and metastasis of HCC |
title_sort | tmem106a transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma: tmem106a is involved in invasion and metastasis of hcc |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827947/ https://www.ncbi.nlm.nih.gov/pubmed/35713314 http://dx.doi.org/10.3724/abbs.2022069 |
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