Identification of ncRNA-Mediated Prognostic Value and Functions of MTHFD2 in Bladder Cancer

Abstract

\n Background: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), one of mitochondrial enzymes, is involved in folate and nucleic acid metabolism and maintains the cellular redox balance. However, the function of MTHFD2 in bladder cancer is still poorly characterized. This study was designed to elucidate the effect and regulatory mechanism of MTHFD2 on bladder cancer cells and explore the relationships between MTHFD2 and immune cell infiltration in tumor microenvironment (TME). Methods: The data from Oncomine, TIMER, The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) database were extracted to evaluate the expression of MTHFD2 and its prognostic role in pan-cancer, especially in bladder cancer. Enrichment analyses, were utilized to explore the underlying cellular mechanisms. The ncRNA regulatory axis was established by Starbase database, and the PPI network was constructed by Cytoscape software. Ultimately, the relations between the expression of MTHFD2 and immune cell infiltration in bladder cancer was indicated by TCGA and TIMER databases.Results: Our results demonstrated that MTHFD2 expression was generally up-regulated in pan-cancers and its high expression was correlated with poor prognosis of patients with bladder cancer. Specifically, our study revealed that MTHFD2 was a powerful risk factor and involved in the tumor development of bladder cancer. Furthermore, hsa_circ_0046140 and hsa_circ_0006769/miR-383-5p/MTHFD2 axis could also play a significant role in tumorigenesis. Ultimately, a strong correlation was observed between MTHFD2 expression and various immune cell infiltration, which implied that MTHFD2 might serve as an agent in tumor immunotherapy. Conclusion: MTHFD2 is widely overexpressed in pan-cancers, and its expression is related with the prognosis of patients and the multiple immune cell infiltrates in TME. Besides, hsa_circ_0046140 and hsa_circ_0006769/miR-383-5p/MTHFD2 axis are implicated with the proliferation and invasion of tumors.