Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a marker for poor prognosis
Abstract Background DIRAS1 is a new member of the Ras gene family. It was described as a potential tumor suppressor in human glioblastomas and esophageal cancer. The role of DIRAS1 in colorectal cancer remains unclear. Methods To explore the epigenetic changes and function of DIRAS1 in human colorec...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13148-017-0348-0 |
| _version_ | 1811301443372580864 |
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| author | Ruipan Zheng Dan Gao Tao He Meiying Zhang Xiaomei Zhang Enqiang Linghu Lixin Wei Mingzhou Guo |
| author_facet | Ruipan Zheng Dan Gao Tao He Meiying Zhang Xiaomei Zhang Enqiang Linghu Lixin Wei Mingzhou Guo |
| author_sort | Ruipan Zheng |
| collection | DOAJ |
| description | Abstract Background DIRAS1 is a new member of the Ras gene family. It was described as a potential tumor suppressor in human glioblastomas and esophageal cancer. The role of DIRAS1 in colorectal cancer remains unclear. Methods To explore the epigenetic changes and function of DIRAS1 in human colorectal cancer, we studied ten colorectal cancer cell lines and 146 primary colorectal cancer samples and 50 matched adjacent samples using semi-quantitative reverse transcription PCR, immunohistochemistry, methylation-specific PCR and bisulfite sequencing, western blot, flow cytometry, and transwell assays. Results DIRAS1 expression was found in DKO and HCT116 cells, while reduced expression was detected in LoVo, SW48, LS180, and SW620 cells, and there was no expression detected in DLD1, HT29, RKO, and SW480 cells. Complete methylation was found in the promoter region of DLD1, HT29, RKO, and SW480 cells. Partial methylation was detected in LoVo, LS180, SW48, and SW620 cells, and unmethylation was found in DKO and HCT116 cells. These results indicate that promoter region methylation correlated with loss of/reduced expression of DIRAS1. Re-expression of DIRAS1 was induced by 5-aza-2′-deoxycytidine, suggesting that the expression of DIRAS1 is regulated by promoter region methylation. DIRAS1 was methylated in 47.3% (69/146) of primary colorectal cancer samples, no methylation was found in non-cancerous colonic tissue samples. Methylation of DIRAS1 was significantly associated with TNM stage (P < 0.05) and short survival time (P = 0.0121). DIRAS1 induced apoptosis and inhibited cell proliferation, migration, and invasion in colorectal cancer. Finally, DIRAS1 suppressed colorectal cancer cell xenograft growth in nude mice. Conclusions DIRAS1 is frequently methylated in human colorectal cancer and the expression of DIRAS1 is regulated by promoter region methylation. Methylation of DIRAS1 is a marker of poor prognosis in human colorectal cancer. |
| first_indexed | 2024-04-13T07:08:55Z |
| format | Article |
| id | doaj.art-3807f8f6dded414c98cc5adc0b62daaa |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-04-13T07:08:55Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-3807f8f6dded414c98cc5adc0b62daaa2022-12-22T02:56:56ZengBMCClinical Epigenetics1868-70751868-70832017-05-01911910.1186/s13148-017-0348-0Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a marker for poor prognosisRuipan Zheng0Dan Gao1Tao He2Meiying Zhang3Xiaomei Zhang4Enqiang Linghu5Lixin Wei6Mingzhou Guo7Department of Gastroenterology and Hepatology, Chinese People’s Liberation Army General HospitalDepartment of Gastroenterology and Hepatology, Chinese People’s Liberation Army General HospitalDepartment of Gastroenterology and Hepatology, Chinese People’s Liberation Army General HospitalDepartment of Gastroenterology and Hepatology, Chinese People’s Liberation Army General HospitalDepartment of Gastroenterology and Hepatology, Chinese People’s Liberation Army General HospitalDepartment of Gastroenterology and Hepatology, Chinese People’s Liberation Army General HospitalDepartment of Pathology, Chinese People’s Liberation Army General HospitalDepartment of Gastroenterology and Hepatology, Chinese People’s Liberation Army General HospitalAbstract Background DIRAS1 is a new member of the Ras gene family. It was described as a potential tumor suppressor in human glioblastomas and esophageal cancer. The role of DIRAS1 in colorectal cancer remains unclear. Methods To explore the epigenetic changes and function of DIRAS1 in human colorectal cancer, we studied ten colorectal cancer cell lines and 146 primary colorectal cancer samples and 50 matched adjacent samples using semi-quantitative reverse transcription PCR, immunohistochemistry, methylation-specific PCR and bisulfite sequencing, western blot, flow cytometry, and transwell assays. Results DIRAS1 expression was found in DKO and HCT116 cells, while reduced expression was detected in LoVo, SW48, LS180, and SW620 cells, and there was no expression detected in DLD1, HT29, RKO, and SW480 cells. Complete methylation was found in the promoter region of DLD1, HT29, RKO, and SW480 cells. Partial methylation was detected in LoVo, LS180, SW48, and SW620 cells, and unmethylation was found in DKO and HCT116 cells. These results indicate that promoter region methylation correlated with loss of/reduced expression of DIRAS1. Re-expression of DIRAS1 was induced by 5-aza-2′-deoxycytidine, suggesting that the expression of DIRAS1 is regulated by promoter region methylation. DIRAS1 was methylated in 47.3% (69/146) of primary colorectal cancer samples, no methylation was found in non-cancerous colonic tissue samples. Methylation of DIRAS1 was significantly associated with TNM stage (P < 0.05) and short survival time (P = 0.0121). DIRAS1 induced apoptosis and inhibited cell proliferation, migration, and invasion in colorectal cancer. Finally, DIRAS1 suppressed colorectal cancer cell xenograft growth in nude mice. Conclusions DIRAS1 is frequently methylated in human colorectal cancer and the expression of DIRAS1 is regulated by promoter region methylation. Methylation of DIRAS1 is a marker of poor prognosis in human colorectal cancer.http://link.springer.com/article/10.1186/s13148-017-0348-0DIRAS1EpigeneticsDNA methylationColorectal cancer |
| spellingShingle | Ruipan Zheng Dan Gao Tao He Meiying Zhang Xiaomei Zhang Enqiang Linghu Lixin Wei Mingzhou Guo Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a marker for poor prognosis Clinical Epigenetics DIRAS1 Epigenetics DNA methylation Colorectal cancer |
| title | Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a marker for poor prognosis |
| title_full | Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a marker for poor prognosis |
| title_fullStr | Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a marker for poor prognosis |
| title_full_unstemmed | Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a marker for poor prognosis |
| title_short | Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a marker for poor prognosis |
| title_sort | methylation of diras1 promotes colorectal cancer progression and may serve as a marker for poor prognosis |
| topic | DIRAS1 Epigenetics DNA methylation Colorectal cancer |
| url | http://link.springer.com/article/10.1186/s13148-017-0348-0 |
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