FTO-CHRM3 axis regulates multiple myeloma progression: a machine learning-based identification.

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Fat Mass and Obesity-Associated (FTO) gene is implicated in multiple myeloma (MM) progression.
• The precise mechanisms of FTO's role in MM remain largely unknown.

Purpose of the Study:

• To investigate the role and mechanisms of FTO in multiple myeloma (MM).
• To identify FTO-associated genes and their impact on the MM immune microenvironment.

Main Methods:

• Machine learning and correlation analyses to identify FTO-associated genes.
• Immunohistochemistry to validate gene expression in MM tissues.
• Immune infiltration and single-cell RNA sequencing (scRNA-seq) to analyze the immune microenvironment and cellular expression patterns.

Main Results:

• FTO is upregulated in MM and linked to poor prognosis.
• Identified CHRM3, GINS3, RRM2, and SHCBP1 as potential FTO-associated genes, with a focus on the FTO-CHRM3 axis.
• FTO and CHRM3 are involved in DNA replication and cell cycle; altered M2 macrophage and eosinophil infiltration observed.
• scRNA-seq revealed monocyte-specific SLC8A1 expression in the calcium signaling pathway.

Conclusions:

• The FTO-CHRM3 axis drives MM progression through calcium signaling pathway dysregulation.
• Understanding these mechanisms provides potential targets for MM interventions.