MTHFD2 Expression Association with Bladder Cancer and Screening of its Potential Inhibitor

Abstract BackgroundBladder cancer is the most common urological malignancy. Genes of folate mediated 1 carbon metabolism are found to be highly up regulated in tumor cells and promotes tumor cell proliferation. Rationale and aim of the studyThe aim of the current study was to determine the expression of MTHFD2 gene and the impact of intronic SNP rs1667627 on MTHFD2 expression Furthermore, determination of potential ligand based inhibitors against MTHFD2. Methods & ResultsSemi-quantitative expression analysis and sanger sequencing were used for this purpose. Moreover, structure based virtual ligand library screening in order to find plausible inhibitors.MTHFD2 expression was significantly increased with tumor stage progression both in low and high-grade bladder cancer. However, the relative fold change difference in low grade bladder cancer in correlation with the tumor stage progression was more dramatic. Contrary to the TCGA dataset analysis, increased MTHFD2 expression was observed in papillary bladder cancer tumor. G to A transition in the intronic variant rs1667627 SNP was determined in tumor tissues as compared to control. Virtual ligand based library screening against the three dimensional MTHFD2 protein lead to identification of a plausible inhibitor MCULE-8027924848 that displayed lower binding free energy as compared to already documented LY345899. ConclusionMTHFD2 might be used as low-grade bladder cancer biomarker since its expression level changes drastically with tumor progression. Further, experimental studies are required to establish the potential mode of inhibition of MCULE-8027924848 ligand.