Hypermethylation of <i>UCHL1</i> Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN)
Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the <i>UCHL1</i> promoter leads to its downr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/3/559 |
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| author | Yin Zhao Yuan Lei Shi-Wei He Ying-Qin Li Ya-Qin Wang Xiao-Hong Hong Ye-Lin Liang Jun-Yan Li Yang Chen Wei-Jie Luo Pan-Pan Zhang Xiao-Jing Yang Qing-Mei He Jun Ma Na Liu Ling-Long Tang |
| author_facet | Yin Zhao Yuan Lei Shi-Wei He Ying-Qin Li Ya-Qin Wang Xiao-Hong Hong Ye-Lin Liang Jun-Yan Li Yang Chen Wei-Jie Luo Pan-Pan Zhang Xiao-Jing Yang Qing-Mei He Jun Ma Na Liu Ling-Long Tang |
| author_sort | Yin Zhao |
| collection | DOAJ |
| description | Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the <i>UCHL1</i> promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment. |
| first_indexed | 2024-03-12T09:50:03Z |
| format | Article |
| id | doaj.art-73481b23e87f4319a5cec38a66fb6579 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T09:50:03Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-73481b23e87f4319a5cec38a66fb65792023-09-02T12:37:16ZengMDPI AGCells2073-44092020-02-019355910.3390/cells9030559cells9030559Hypermethylation of <i>UCHL1</i> Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN)Yin Zhao0Yuan Lei1Shi-Wei He2Ying-Qin Li3Ya-Qin Wang4Xiao-Hong Hong5Ye-Lin Liang6Jun-Yan Li7Yang Chen8Wei-Jie Luo9Pan-Pan Zhang10Xiao-Jing Yang11Qing-Mei He12Jun Ma13Na Liu14Ling-Long Tang15Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, ChinaEpigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the <i>UCHL1</i> promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment.https://www.mdpi.com/2073-4409/9/3/559nasopharyngeal carcinomauchl1metastasismethylationcttn |
| spellingShingle | Yin Zhao Yuan Lei Shi-Wei He Ying-Qin Li Ya-Qin Wang Xiao-Hong Hong Ye-Lin Liang Jun-Yan Li Yang Chen Wei-Jie Luo Pan-Pan Zhang Xiao-Jing Yang Qing-Mei He Jun Ma Na Liu Ling-Long Tang Hypermethylation of <i>UCHL1</i> Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN) Cells nasopharyngeal carcinoma uchl1 metastasis methylation cttn |
| title | Hypermethylation of <i>UCHL1</i> Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN) |
| title_full | Hypermethylation of <i>UCHL1</i> Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN) |
| title_fullStr | Hypermethylation of <i>UCHL1</i> Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN) |
| title_full_unstemmed | Hypermethylation of <i>UCHL1</i> Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN) |
| title_short | Hypermethylation of <i>UCHL1</i> Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN) |
| title_sort | hypermethylation of i uchl1 i promotes metastasis of nasopharyngeal carcinoma by suppressing degradation of cortactin cttn |
| topic | nasopharyngeal carcinoma uchl1 metastasis methylation cttn |
| url | https://www.mdpi.com/2073-4409/9/3/559 |
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