TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma
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...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-06-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022069 |
| _version_ | 1797635381824323584 |
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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 | DOAJ |
| 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. |
| first_indexed | 2024-03-11T12:21:16Z |
| format | Article |
| id | doaj.art-eb9a6744ad3f4f3291647f1c2601c6ea |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:21:16Z |
| publishDate | 2022-06-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-eb9a6744ad3f4f3291647f1c2601c6ea2023-11-07T01:00:39ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-06-01541008102010.3724/abbs.202206920d259ccTMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinomaShi Shiming0Wang Biao1Wan Jinglei2Song Lina3Zhu Guiqi4Du Junxian5Ye Luxi6Zhao Qianqian7Cai Jialiang8Chen Qing9Xiao Kun10He Jian11Yu Lei12Dai Zhi13["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China","Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China","Department of Pediatric Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China","Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China"]["Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"]["Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China"]["Department of General Surgery, Zhongshan Hospital (South), Fudan University, Shanghai Public Health Clinical Center, Fudan University, Shanghai 200083, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China","Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China"]["Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China","Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China"]["Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China"]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.https://www.sciengine.com/doi/10.3724/abbs.2022069hepatocellular carcinomatransmembrane protein 106Amethylationepithelial mesenchymal transitionmetastasis |
| spellingShingle | 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 Acta Biochimica et Biophysica Sinica hepatocellular carcinoma transmembrane protein 106A methylation epithelial mesenchymal transition metastasis |
| title | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma |
| title_full | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma |
| title_fullStr | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma |
| title_full_unstemmed | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma |
| title_short | TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma |
| title_sort | tmem106a transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma |
| topic | hepatocellular carcinoma transmembrane protein 106A methylation epithelial mesenchymal transition metastasis |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022069 |
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