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Comprehensive Analysis Identifies Hsa_circ_0058191 as a Potential Drug Resistance Target in Multiple Myeloma
Huiye Yang1, Jie Zhu1, Xiaotao Wang1
1Department of Hematology, The Affiliated Hospital of Guilin Medical University, Guilin, People's Republic of China.
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.
Insights
This study identifies hsa_circ_0058191 as a key circular RNA driving bortezomib resistance in multiple myeloma (MM). Understanding this mechanism offers new therapeutic targets for overcoming drug resistance in MM patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multiple Myeloma (MM) is a prevalent hematologic malignancy known for its resistance to bortezomib, a first-line treatment.
- Circular RNAs (circRNAs) are implicated in cancer drug resistance, but their specific roles in MM remain largely uncharacterized.
Purpose of the Study:
- To identify and investigate circRNAs involved in bortezomib resistance in Multiple Myeloma.
- To elucidate the molecular mechanisms underlying circRNA-mediated drug resistance in MM.
Main Methods:
- Screening of circRNAs from bortezomib-resistant MM patients using microarrays.
- Bioinformatic analysis of public MM datasets (GEO database) to identify candidate circRNAs.
- Validation of circRNA expression via qRT-PCR and prediction of miRNA/RBP interactions using CircInteractome and Metascape.
Main Results:
- hsa_circ_0058191 was significantly overexpressed in bortezomib-resistant MM samples.
- hsa_circ_0058191 interacts with miR-660 and AGO2, regulating RNA modification and mRNA pathways.
- These interactions provide insights into the molecular basis of drug resistance in MM.
Conclusions:
- hsa_circ_0058191 plays a crucial role in the development of bortezomib resistance in Multiple Myeloma.
- This finding provides a theoretical basis for developing novel therapeutic strategies to combat drug resistance in MM.
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