Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion
Cervical cancer (CC) remains one of the leading causes of cancer-related deaths worldwide. However, cervical cancer is preceded by the pre-malignant cervical intraepithelial neoplasia (CIN) that can last for up to 20 years before becoming malignant. Therefore, early screening is the key to prevent t...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1010132/full |
| _version_ | 1811169927539720192 |
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| author | Peng Zhu Peng Zhu Peng Zhu Xiang Li Yujie Liu Yujie Liu Yujie Liu Jing Xiong Ding Yuan Yan Chen Yan Chen Yan Chen Yan Chen Lili Luo Ju Huang Binbin Wang Quanfang Nie Shuli Wang Liying Dang Shu Li Yan Shu Yan Shu Yan Shu Wei Zhang Wei Zhang Wei Zhang Honghao Zhou Honghao Zhou Honghao Zhou Lan Fan Lan Fan Lan Fan Qing Li Qing Li Qing Li |
| author_facet | Peng Zhu Peng Zhu Peng Zhu Xiang Li Yujie Liu Yujie Liu Yujie Liu Jing Xiong Ding Yuan Yan Chen Yan Chen Yan Chen Yan Chen Lili Luo Ju Huang Binbin Wang Quanfang Nie Shuli Wang Liying Dang Shu Li Yan Shu Yan Shu Yan Shu Wei Zhang Wei Zhang Wei Zhang Honghao Zhou Honghao Zhou Honghao Zhou Lan Fan Lan Fan Lan Fan Qing Li Qing Li Qing Li |
| author_sort | Peng Zhu |
| collection | DOAJ |
| description | Cervical cancer (CC) remains one of the leading causes of cancer-related deaths worldwide. However, cervical cancer is preceded by the pre-malignant cervical intraepithelial neoplasia (CIN) that can last for up to 20 years before becoming malignant. Therefore, early screening is the key to prevent the progression of cervical lesions into invasive cervical cancer and decrease the incidence. The genes, down-regulated and hypermethylated in cancers, may provide potential drug targets for cervical cancer. In our current study, using the datasets from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, we found that endothelin 3 (EDN3) was downregulated and hypermethylated in cervical squamous cell carcinoma (CSCC). The further analysis in GSE63514 (n=128) dataset and in our samples (n=221) found that the expression of EDN3 was decreased with the degree of cervical lesions. Pyrosequencing was performed to evaluate 4 CpG sites of the EDN3 promoter region in our samples (n=469). The data indicated that the methylation level of EDN3 was increased with the degree of cervical lesions. EDN3 silencing mediated by methylation can be blocked by 5-Azacytidine (5-Aza), a DNA methyltransferase 1 (DNMT1) inhibitor, treatment in cervical cancer cell lines. Ethynyldeoxyuridine (EdU) assay, would-healing assay, clone formation assay and transwell assay were conducted to investigate the biological function of EDN3 in cervical cancer cell lines. The results of these experiments confirmed that overexpression of EDN3 could inhibit the proliferation, clone formation, migration and invasion of cervical cancer cells. EDN3 may provide potential biomarker and therapeutic target for CSCC. |
| first_indexed | 2024-04-10T16:50:12Z |
| format | Article |
| id | doaj.art-c83473e88c834e988a76932186943724 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T16:50:12Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c83473e88c834e988a769321869437242023-02-07T17:41:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-02-011310.3389/fonc.2023.10101321010132Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasionPeng Zhu0Peng Zhu1Peng Zhu2Xiang Li3Yujie Liu4Yujie Liu5Yujie Liu6Jing Xiong7Ding Yuan8Yan Chen9Yan Chen10Yan Chen11Yan Chen12Lili Luo13Ju Huang14Binbin Wang15Quanfang Nie16Shuli Wang17Liying Dang18Shu Li19Yan Shu20Yan Shu21Yan Shu22Wei Zhang23Wei Zhang24Wei Zhang25Honghao Zhou26Honghao Zhou27Honghao Zhou28Lan Fan29Lan Fan30Lan Fan31Qing Li32Qing Li33Qing Li34Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaDepartment of Gynaecology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaDepartment of Gynaecology and Obstetrics, The Second Xiangya Hospital, Central South University, Changsha, ChinaHealth Management Center, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaXiangya Medical Laboratory, Central South University, Changsha, ChinaDepartment of Gynaecology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Gynaecology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Obstetrics and Gynecology, Loudi Central Hospital, Loudi, ChinaDepartment of Obstetrics and Gynecology, Loudi Central Hospital, Loudi, China0Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China0Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, ChinaXiangya Medical Laboratory, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaCervical cancer (CC) remains one of the leading causes of cancer-related deaths worldwide. However, cervical cancer is preceded by the pre-malignant cervical intraepithelial neoplasia (CIN) that can last for up to 20 years before becoming malignant. Therefore, early screening is the key to prevent the progression of cervical lesions into invasive cervical cancer and decrease the incidence. The genes, down-regulated and hypermethylated in cancers, may provide potential drug targets for cervical cancer. In our current study, using the datasets from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, we found that endothelin 3 (EDN3) was downregulated and hypermethylated in cervical squamous cell carcinoma (CSCC). The further analysis in GSE63514 (n=128) dataset and in our samples (n=221) found that the expression of EDN3 was decreased with the degree of cervical lesions. Pyrosequencing was performed to evaluate 4 CpG sites of the EDN3 promoter region in our samples (n=469). The data indicated that the methylation level of EDN3 was increased with the degree of cervical lesions. EDN3 silencing mediated by methylation can be blocked by 5-Azacytidine (5-Aza), a DNA methyltransferase 1 (DNMT1) inhibitor, treatment in cervical cancer cell lines. Ethynyldeoxyuridine (EdU) assay, would-healing assay, clone formation assay and transwell assay were conducted to investigate the biological function of EDN3 in cervical cancer cell lines. The results of these experiments confirmed that overexpression of EDN3 could inhibit the proliferation, clone formation, migration and invasion of cervical cancer cells. EDN3 may provide potential biomarker and therapeutic target for CSCC.https://www.frontiersin.org/articles/10.3389/fonc.2023.1010132/fullEDN3DNA methylationcervical cancerCINbiomarker |
| spellingShingle | Peng Zhu Peng Zhu Peng Zhu Xiang Li Yujie Liu Yujie Liu Yujie Liu Jing Xiong Ding Yuan Yan Chen Yan Chen Yan Chen Yan Chen Lili Luo Ju Huang Binbin Wang Quanfang Nie Shuli Wang Liying Dang Shu Li Yan Shu Yan Shu Yan Shu Wei Zhang Wei Zhang Wei Zhang Honghao Zhou Honghao Zhou Honghao Zhou Lan Fan Lan Fan Lan Fan Qing Li Qing Li Qing Li Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion Frontiers in Oncology EDN3 DNA methylation cervical cancer CIN biomarker |
| title | Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion |
| title_full | Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion |
| title_fullStr | Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion |
| title_full_unstemmed | Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion |
| title_short | Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion |
| title_sort | methylation mediated silencing of edn3 promotes cervical cancer proliferation migration and invasion |
| topic | EDN3 DNA methylation cervical cancer CIN biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1010132/full |
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