CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties
Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon ca...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-06-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.708038/full |
| _version_ | 1819289636997955584 |
|---|---|
| author | Shudong Zhu Shudong Zhu Shudong Zhu Yan Zhu Yan Zhu Qiuwen Wang Yi Zhang Xialing Guo |
| author_facet | Shudong Zhu Shudong Zhu Shudong Zhu Yan Zhu Yan Zhu Qiuwen Wang Yi Zhang Xialing Guo |
| author_sort | Shudong Zhu |
| collection | DOAJ |
| description | Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells. |
| first_indexed | 2024-12-24T03:10:00Z |
| format | Article |
| id | doaj.art-8d34e56239664a52b3c008402f073c9b |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-24T03:10:00Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-8d34e56239664a52b3c008402f073c9b2022-12-21T17:17:51ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-06-01910.3389/fcell.2021.708038708038CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic PropertiesShudong Zhu0Shudong Zhu1Shudong Zhu2Yan Zhu3Yan Zhu4Qiuwen Wang5Yi Zhang6Xialing Guo7School of Medicine, Nantong University, Nantong, ChinaDepartment of Biochemistry and Molecular Biology, School of Life Science, Central South University, Changsha, ChinaXuzhou Health Research Institute, Xuzhou, ChinaSchool of Medicine, Nantong University, Nantong, ChinaXuzhou Health Research Institute, Xuzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Life Science, Central South University, Changsha, ChinaDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, School of Life Science, Central South University, Changsha, ChinaArgus Pharmaceuticals, Changsha, ChinaSrc is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.https://www.frontiersin.org/articles/10.3389/fcell.2021.708038/fullCHKcolon cancerDNA methylationFHCdrug resistance |
| spellingShingle | Shudong Zhu Shudong Zhu Shudong Zhu Yan Zhu Yan Zhu Qiuwen Wang Yi Zhang Xialing Guo CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties Frontiers in Cell and Developmental Biology CHK colon cancer DNA methylation FHC drug resistance |
| title | CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties |
| title_full | CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties |
| title_fullStr | CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties |
| title_full_unstemmed | CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties |
| title_short | CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties |
| title_sort | chk methylation is elevated in colon cancer cells and contributes to the oncogenic properties |
| topic | CHK colon cancer DNA methylation FHC drug resistance |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.708038/full |
| work_keys_str_mv | AT shudongzhu chkmethylationiselevatedincoloncancercellsandcontributestotheoncogenicproperties AT shudongzhu chkmethylationiselevatedincoloncancercellsandcontributestotheoncogenicproperties AT shudongzhu chkmethylationiselevatedincoloncancercellsandcontributestotheoncogenicproperties AT yanzhu chkmethylationiselevatedincoloncancercellsandcontributestotheoncogenicproperties AT yanzhu chkmethylationiselevatedincoloncancercellsandcontributestotheoncogenicproperties AT qiuwenwang chkmethylationiselevatedincoloncancercellsandcontributestotheoncogenicproperties AT yizhang chkmethylationiselevatedincoloncancercellsandcontributestotheoncogenicproperties AT xialingguo chkmethylationiselevatedincoloncancercellsandcontributestotheoncogenicproperties |