Comprehensive Analysis Identifies Hsa_circ_0058191 as a Potential Drug Resistance Target in Multiple Myeloma.

Abstract

Background: Multiple Myeloma (MM) is the second most common hematologic malignancy, which exhibits strong resistance to bortezomib, the first-line treatment. Circular RNAs (circRNAs) are increasingly considered as important drivers of drug resistance across various cancers, but their roles in multiple myeloma are not well understood.

Aim: To investigate and identify potential circRNA targets and their roles in the mechanisms of bortezomib resistance.

Methods: Bortezomib-resistant MM patient-specific circRNAs were screened using Arraystar circRNA microarrays. The MM circRNA dataset from the GEO database was analyzed with GEO2R to identify candidate circRNAs associated with MM progression and drug resistance. CircRNA-forming and loop-forming sites, along with their structures, were identified via Sanger sequencing. The identified circRNA was validated by qRT-PCR in MM patients with and without bortezomib resistance. Bioinformatic analysis through CircInteractome was conducted to predict potential miRNA and RBP binding for the core circRNAs. Metascape was employed to perform RBP pathway analysis to identify specific biological processes in circRNAs.

Results: The hsa_circ_0058191 was found to be overexpressed in bortezomib-resistant MM patient samples, suggesting its pivotal role in drug resistance mechanisms. The interaction of hsa_circ_0058191 with miR-660 and AGO2 as determined through bioinformatic predictions, indicated that it regulates RNA modification and mRNA regulation pathways. These molecular interactions expand our understanding of the mechanisms of drug resistance in multiple myeloma.

Conclusion: This study identified the role of hsa_circ_0058191 in the development of drug resistance in MM, which provides a theoretical foundation for designing potential therapeutic strategies to prevent drug resistance.