METTL25 EXPRESSION PROFILING ACROSS HUMAN TISSUES AND CANCERS

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Abstract
Background: Although recent studies have established the critical roles of methyltransferases in epigenetic regulation and cellular homeostasis, the biological function of METTL25, a member of this enzyme family, is not well known. Current clinical research has identified various methyltransferases as key regulators of gene expression, yet METTL25 remains functionally uncharacterized, representing a significant knowledge gap in our understanding of methyltransferase biology. Objective: This study examines the expression patterns of METTL25 across normal human tissues and cancer contexts to identify its potential physiological and pathological roles and to understand its regulatory mechanisms in health and disease. Methods: We conducted a systematic computational analysis using large-scale publicly available transcriptomic and proteomic datasets. Expression patterns were analyzed across normal human tissues and cancer cell lines. Correlation analysis between mRNA and protein levels was performed, followed by differential gene expression analysis comparing thyroid carcinoma to normal thyroid tissue. Functional enrichment analysis was applied to identify biological pathways associated with METTL25 expression. Results: METTL25 exhibited tissue-specific expression patterns with highest expression observed in endocrine organs (thyroid, adrenal glands) and immune compartments (lymphoid tissues). Moderate correlation between mRNA and protein levels was identified (r=0.404 ; p=0.001), indicating transcriptional control of protein abundance. METTL25 expression was significantly downregulated in thyroid carcinoma compared to normal thyroid tissue (p<0.01). Higher METTL25 expression in tumors was statistically significant and positively correlated with gene signatures related to wound healing, coagulation, and hemostasis pathways. Conclusion: METTL25 functions as a tissue-restricted methyltransferase with tumor suppressor characteristics in thyroid cancer. The positive correlation between METTL25 expression and wound healing pathways was statistically significant, suggesting its involvement in tissue repair mechanisms. These findings provide the foundation for future mechanistic studies investigating METTL25's role in cancer biology and its potential as a therapeutic target.