Frontiers in Oncology (Feb 2023)
Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion
- 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
Affiliations
- Peng Zhu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Peng Zhu
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Peng Zhu
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Xiang Li
- Department of Gynaecology, The Third Xiangya Hospital, Central South University, Changsha, China
- Yujie Liu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Yujie Liu
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Yujie Liu
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Jing Xiong
- Department of Gynaecology and Obstetrics, The Second Xiangya Hospital, Central South University, Changsha, China
- Ding Yuan
- Health Management Center, Xiangya Hospital, Central South University, Changsha, China
- Yan Chen
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Yan Chen
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Yan Chen
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Yan Chen
- Xiangya Medical Laboratory, Central South University, Changsha, China
- Lili Luo
- Department of Gynaecology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Ju Huang
- Department of Gynaecology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Binbin Wang
- Department of Obstetrics and Gynecology, Loudi Central Hospital, Loudi, China
- Quanfang Nie
- Department of Obstetrics and Gynecology, Loudi Central Hospital, Loudi, China
- Shuli Wang
- 0Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
- Liying Dang
- 0Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
- Shu Li
- Xiangya Medical Laboratory, Central South University, Changsha, China
- Yan Shu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Yan Shu
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Yan Shu
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Wei Zhang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Wei Zhang
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Wei Zhang
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Honghao Zhou
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Honghao Zhou
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Honghao Zhou
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Lan Fan
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Lan Fan
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Lan Fan
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Qing Li
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Qing Li
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Qing Li
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- DOI
- https://doi.org/10.3389/fonc.2023.1010132
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
