Exploring m7G modification to identify a novel gene target associated with cancer

Abstract

m7G modification, methylated by m7G writers, play a critical role in regulating gene expression. Recent studies have shown that aberrant expression of m7G modification and its writers contributes to cancer progression and results in worse patient survival in several human cancers. However, a systematic study that assesses the frequency and clinical relevance of aberrant m7G writer expression in a pan-cancer cohort has yet to be conducted. Therefore, this study aims to systematically investigate the molecular alteration and clinical relevance of m7G methyltransferase in human cancers and further validate the role of m7G modification in particular cancers exhibiting abnormal genetic alterations and significant clinical associations with m7G writers.

Our findings indicate that m7G writers are dysregulated in various cancers and are predominantly associated with poorer survival outcomes. Notably, we observe that aberrant expression of all m7G writers is strongly associated with patient survival in kidney renal clear cell carcinoma (KIRC).

We further investigate the role of m7G writers in KIRC, focusing on METTL1 and WBSCR22. Both METTL1 and WBSCR22 are overexpressed in advanced KIRC and are associated with worse overall survival. By performing knockdown studies in vitro, we found that depletion of METTL1 or WBSCR22 suppresses cell proliferation, colony formation and migration in KIRC cell lines, indicating their oncogenic role in KIRC. Additionally, we find that METTL1 and WBSCR22 expression is negatively correlated with the expression of key tumour suppressor genes commonly dysregulated in KIRC.

Our study provides insights into the potential utility of m7G writer expression as a cancer biomarker and proposes targeting m7G writers as a therapeutic strategy. We highlight the oncogenic role of METTL1 and WBSCR22 in KIRC and their potential as prognostic biomarkers and therapeutic targets.