Published online Jan 24, 2024. doi: 10.5306/wjco.v15.i1.115
Peer-review started: November 20, 2023
First decision: December 5, 2023
Revised: December 13, 2023
Accepted: January 2, 2024
Article in press: January 2, 2024
Published online: January 24, 2024
Multiple myeloma (MM) is a terminally differentiated B-cell tumor disease with a challenging prognosis. Specifically, the t(4;14) MM is categorized as a high-risk subtype within MM.
The t(4;14) MM tends to relapse, and currently, there is a lack of effective clinical treatment strategies.
This study aimed to elucidate the molecular basis of the t(4;14) MM and search for potential effective drugs through a comprehensive approach.
The transcriptional characteristics of t(4;14) multiple myeloma were obtained from the Gene Expression Omnibus and subjected to gene ontology and pathway enrichment analysis. Utilizing the STRING database and Cytoscape, a protein-protein interaction network was constructed, and core targets were identified. Connectivity Map identified potential small-molecule drugs, and these findings were validated through molecular docking analysis. One of these drugs, ivermectin, was further tested for its effects on t(4;14) multiple myeloma cells.
We identified 258 differentially expressed genes with enriched functions in cancer pathways, cytokine receptor interactions, the nuclear factor (NF)-kappa B signaling pathway. Ten key genes were pinpointed. Ivermectin emerged as a potential treatment. In vitro, ivermectin inhibited t(4;14) MM cell growth via the NF-kappa B pathway and induced t(4;14) MM cell apoptosis.
Ivermectin induced apoptosis in t(4;14) MM cells via the NF-κB signaling pathway.
Our study offers valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment.