MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway
Abstract Background While molecular targeted drugs and other therapies are being developed for many tumors, pancreatic cancer is still considered to be the malignant tumor with the worst prognosis. We started this study to identify prognostic genes and therapeutic targets of pancreatic cancer. Metho...
| Main Authors: | , , , , , |
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| Format: | Article |
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BMC
2023-01-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-10433-6 |
| _version_ | 1811175800866603008 |
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| author | Shoichiro Tange Tomomi Hirano Masashi Idogawa Eishu Hirata Issei Imoto Takashi Tokino |
| author_facet | Shoichiro Tange Tomomi Hirano Masashi Idogawa Eishu Hirata Issei Imoto Takashi Tokino |
| author_sort | Shoichiro Tange |
| collection | DOAJ |
| description | Abstract Background While molecular targeted drugs and other therapies are being developed for many tumors, pancreatic cancer is still considered to be the malignant tumor with the worst prognosis. We started this study to identify prognostic genes and therapeutic targets of pancreatic cancer. Methods To comprehensively identify prognostic genes in pancreatic cancer, we investigated the correlation between gene expression and cancer-specific prognosis using transcriptome and clinical information datasets from The Cancer Genome Atlas (TCGA). In addition, we examined the effects of the suppression of candidate prognostic genes in pancreatic cancer cell lines. Result We found that patients with high expression levels of MYEOV, a primate-specific gene with unknown function, had significantly shorter disease-specific survival times than those with low expression levels. Cox proportional hazards analysis revealed that high expression of MYEOV was significantly associated with poor survival and was an independent prognostic factor for disease-specific survival in pancreatic cancer patients. Analysis of multiple cancer samples revealed that the MYEOV promoter region is methylated in noncancer tissues but is demethylated in tumors, causing MYEOV overexpression in tumors. Notably, the knockdown of MYEOV suppressed the expression of MTHFD2 and other folate metabolism-related enzyme genes required for the synthesis of amino acids and nucleic acids and also restored the expression of c-Myc and mTORC1 repressors. Conclusion There is a significant correlation between elevated MYEOV expression and poor disease-specific survival in pancreatic cancer patients. MYEOV enhances the activation of several oncogenic pathways, resulting in the induction of pancreatic cancer cell proliferation. Overall, MYEOV acts as an oncogene in pancreatic cancer. Furthermore, MYEOV may be a prognostic biomarker and serve as an ‘actionable’ therapeutic target for pancreatic cancers. |
| first_indexed | 2024-04-10T19:41:46Z |
| format | Article |
| id | doaj.art-3c032f0a7eea41aa860d0b05651d923c |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-10T19:41:46Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-3c032f0a7eea41aa860d0b05651d923c2023-01-29T12:14:51ZengBMCBMC Cancer1471-24072023-01-0123111210.1186/s12885-022-10433-6MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathwayShoichiro Tange0Tomomi Hirano1Masashi Idogawa2Eishu Hirata3Issei Imoto4Takashi Tokino5Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDivision of Tumor Cell Biology and Bioimaging, Cancer Research Institute, Kanazawa UniversityAichi Cancer Center Research InstituteDepartment of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineAbstract Background While molecular targeted drugs and other therapies are being developed for many tumors, pancreatic cancer is still considered to be the malignant tumor with the worst prognosis. We started this study to identify prognostic genes and therapeutic targets of pancreatic cancer. Methods To comprehensively identify prognostic genes in pancreatic cancer, we investigated the correlation between gene expression and cancer-specific prognosis using transcriptome and clinical information datasets from The Cancer Genome Atlas (TCGA). In addition, we examined the effects of the suppression of candidate prognostic genes in pancreatic cancer cell lines. Result We found that patients with high expression levels of MYEOV, a primate-specific gene with unknown function, had significantly shorter disease-specific survival times than those with low expression levels. Cox proportional hazards analysis revealed that high expression of MYEOV was significantly associated with poor survival and was an independent prognostic factor for disease-specific survival in pancreatic cancer patients. Analysis of multiple cancer samples revealed that the MYEOV promoter region is methylated in noncancer tissues but is demethylated in tumors, causing MYEOV overexpression in tumors. Notably, the knockdown of MYEOV suppressed the expression of MTHFD2 and other folate metabolism-related enzyme genes required for the synthesis of amino acids and nucleic acids and also restored the expression of c-Myc and mTORC1 repressors. Conclusion There is a significant correlation between elevated MYEOV expression and poor disease-specific survival in pancreatic cancer patients. MYEOV enhances the activation of several oncogenic pathways, resulting in the induction of pancreatic cancer cell proliferation. Overall, MYEOV acts as an oncogene in pancreatic cancer. Furthermore, MYEOV may be a prognostic biomarker and serve as an ‘actionable’ therapeutic target for pancreatic cancers.https://doi.org/10.1186/s12885-022-10433-6TCGAPancreatic cancerDNA methylationC-MycmTORC1 |
| spellingShingle | Shoichiro Tange Tomomi Hirano Masashi Idogawa Eishu Hirata Issei Imoto Takashi Tokino MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway BMC Cancer TCGA Pancreatic cancer DNA methylation C-Myc mTORC1 |
| title | MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway |
| title_full | MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway |
| title_fullStr | MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway |
| title_full_unstemmed | MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway |
| title_short | MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway |
| title_sort | myeov overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle c myc mtorc1 pathway |
| topic | TCGA Pancreatic cancer DNA methylation C-Myc mTORC1 |
| url | https://doi.org/10.1186/s12885-022-10433-6 |
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