Prognostic Values of EPDR1 Hypermethylation and Its Inhibitory Function on Tumor Invasion in Colorectal Cancer
| Autor: | Hsiu Hua Wang, Shih Ching Chang, Shung Haur Yang, Te-Chang Lee, Kuo-Chu Lai, Chun Ho Chu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer EPDR1 methylation Biology lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Epidermal growth factor medicine neoplasms MSI Gene knockdown Kinase Microsatellite instability Methylation Transforming growth factor beta medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens invasion digestive system diseases CRC 030104 developmental biology Oncology 030220 oncology & carcinogenesis DNA methylation Cancer research biology.protein prognosis |
| Zdroj: | Cancers Volume 10 Issue 10 Cancers, Vol 10, Iss 10, p 393 (2018) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers10100393 |
| Popis: | Aberrant DNA methylation is a potential mechanism underlying the development of colorectal cancer (CRC). Thus, identification of prognostic DNA methylation markers and understanding the related molecular functions may offer a new perspective on CRC pathogenesis. To that end, we explored DNA methylation profile changes in CRC subtypes based on the microsatellite instability (MSI) status through genome-wide DNA methylation profiling analysis. Of 34 altered genes, three hypermethylated (epidermal growth factor, EGF carbohydrate sulfotransferase 10, CHST10 ependymin related 1, EPDR1) and two hypomethylated (bone marrow stromal antigen 2, BST2 Rac family small GTPase 3, RAC3) candidates were further validated in CRC patients. Based on quantitative methylation-specific polymerase chain reaction (Q-MSP), EGF, CHST10 and EPDR1 showed higher hypermethylated levels in CRC tissues than those in adjacent normal tissues, whereas BST2 showed hypomethylation in CRC tissues relative to adjacent normal tissues. Additionally, among 75 CRC patients, hypermethylation of CHST10 and EPDR1 was significantly correlated with the MSI status and a better prognosis. Moreover, EPDR1 hypermethylation was significantly correlated with node negativity and a lower tumor stage as well as with mutations in B-Raf proto-oncogene serine/threonine kinase (BRAF) and human transforming growth factor beta receptor 2 (TGF&beta R2). Conversely, a negative correlation between the mRNA expression and methylation levels of EPDR1 in CRC tissues and cell lines was observed, revealing that DNA methylation has a crucial function in modulating EPDR1 expression in CRC cells. EPDR1 knockdown by a transient small interfering RNA significantly suppressed invasion by CRC cells, suggesting that decreased EPDR1 levels may attenuate CRC cell invasion. These results suggest that DNA methylation-mediated EPDR1 epigenetic silencing may play an important role in preventing CRC progression. |
| Databáze: | OpenAIRE |
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