Fat Mass and Obesity-Associated (FTO) is linked to multiple myeloma (MM) progression, but its action mechanisms are poorly understood. Machine learning and correlation analysis identified genes with consistent expression patterns as FTO-associated genes. Additionally, the expression levels of FTO and its associated genes in MM tissues were validated through immunohistochemistry. The impact of FTO-associated genes expression on the immune microenvironment of MM was assessed through immune infiltration analysis. Single-cell RNA sequencing (scRNA-seq) elucidated cellular expression patterns. FTO was found to be significantly upregulated in MM and associated with poor prognosis. Four potential FTO-associated genes (CHRM3, GINS3, RRM2, and SHCBP1) were identified. Correlation and immunohistochemical analyses further focused the FTO-CHRM3 axis. Functional enrichment analysis unveiled that FTO and CHRM3 were involved in “DNA replication” and “cell cycle”. The infiltration of M2 macrophages and eosinophils were altered in high FTO/CHRM3 expression groups. ScRNA-seq highlighted the monocyte-specific expression of SLC8A1 in the calcium signaling pathway in MM. The FTO-CHRM3 axis contributes to MM progression via calcium signaling pathway dysregulation, and the exploration of its underlying mechanisms provides insights for targeted MM interventions.
Lü et al. (Mon,) studied this question.