Up-regulation of MTHFD2 is associated with clinicopathological characteristics and poor survival in ovarian cancer, possibly by regulating MOB1A signaling
| Autor: | Sanyuan Zhang, Jiaolin Yang, Xuan Jing, Xueqing Wu, Xiangrong Cui, Kai Huo, Huancheng Su |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Mutation Missense Gene Expression Young Adult Lymphocytes Tumor-Infiltrating Downregulation and upregulation Ovarian cancer Aminohydrolases Cell Movement Cell Line Tumor Databases Genetic Medicine Humans Neoplasm Invasiveness Adaptor Proteins Signal Transducing Aged Cell Proliferation Methylenetetrahydrofolate Dehydrogenase (NADP) Ovarian Neoplasms MTHFD2 business.industry Obstetrics and Gynecology Computational Biology Gynecology and obstetrics Middle Aged medicine.disease Prognosis Multifunctional Enzymes Up-Regulation Survival Rate Oncology Gene Knockdown Techniques MOB1A RG1-991 Cancer research Female business Signal Transduction |
| Zdroj: | Journal of Ovarian Research, Vol 15, Iss 1, Pp 1-14 (2022) |
| ISSN: | 1757-2215 |
| Popis: | Background MTHFD2 is a folate-coupled metabolic enzyme, which has been proved to participant in the metabolic reprogramming and tumor cell-sustaining proliferative capacity. However, the function of MTHFD2 in the development of ovarian cancer and its potential molecular mechanisms is still unclear. Materials and methods The expression, various mutations, prognosis, and related network signaling pathways of MTHFD2 were analyzed using bioinformatics-related websites, including Oncomine, GEPIA, UCSC, cBioPortal, KM Plotter, TISIDB and TIMER. The prognostic value of MTHFD2 expression was validated by our own ovarian cancer samples using RT-qPCR. The migration ad invasion of ovarian cancer cells were further analyzed by CCK-8 and transwell assay. The Western-blot assay was performed to explore the protein levels of MTHFD2 and MOB1A. Results We obtained the following important results. (1) MTHFD2 expression was markedly up-regulated in ovarian cancer than normal samples. (2) Among patients with ovarian cancer, those with higher MTHFD2 expression was associated with lower survival rate. (3) The major mutation type of MTHFD2 in ovarian cancer samples was missense mutation. (4) MTHFD2 knockdown inhibited proliferation, migration, invasion, as well as the expression of MOB1A in vitro. Conclusion MTHFD2, as a NAD + -dependent enzyme, accelerated tumor progression by up-regulating MBO1A, suggesting that this protein may be an independent prognostic factor and a potential therapeutic target for future ovarian cancer treatments. |
| Databáze: | OpenAIRE |
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