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CircRNA Microarray Profiling Reveals hsa_circ_0058493 as a Novel Biomarker for Imatinib-Resistant CML
An-Ni Zhong1,2,3, Yi Yin1,2, Bing-Jie Tang1,2
1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Background: CircRNA has appeared as a critical molecular in the development of various cancers. However, the cellular function of circRNAs and exosomal circRNAs has not been well explored in Chronic myeloid leukemia (CML). Methods: Differentially expressed circRNAs were identified by a human circRNA microarray analysis. The expression of hsa_circ_0058493 in peripheral blood mononuclear cells (PBMCs) and exosomes was verified using quantitative real-time PCR. Short hairpin RNAs against hsa_circ_0058493 were constructed to silence the expression of circ_0058493. CCK8, flow cytometry and EdU assay were performed to investigate the biological functions of circ_0058493. Results: Hsa_circ_0058493 was significantly overexpressed in the PBMCs of CML patients and high level of circ_0058493 was associated with the poor clinical efficacy of imatinib. Silencing the expression of circ_0058493 significantly inhibited the development of imatinib-resistant CML cells. miR-548b-3p was overexpressed in circ_0058493-downregulated CML cells. Bioinformatic analysis revealed that circ_0058493 might exert its regulatory function acting as a "sponge" of miR-548b-3p. Moreover, hsa_circ_0058493 was significantly enriched in the exosomes derived from imatinib-resistant CML cells. Conclusion: Hsa_circ_0058493 in PBMCs could be a promising prognostic biomarker and might provide a therapeutic target for CML treatment.
Insights
Circular RNA hsa_circ_0058493 is overexpressed in Chronic myeloid leukemia (CML) and promotes imatinib resistance. This circRNA may serve as a prognostic biomarker and therapeutic target for CML treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Circular RNAs (circRNAs) play roles in various cancers, but their function in Chronic Myeloid Leukemia (CML) remains unclear.
- Exosomal circRNAs and their specific roles in CML pathogenesis are not well understood.
- Investigating novel molecular mechanisms in CML is crucial for improving treatment strategies.
Purpose of the Study:
- To identify differentially expressed circRNAs in CML.
- To explore the cellular and exosomal functions of hsa_circ_0058493 in CML.
- To evaluate hsa_circ_0058493 as a potential prognostic biomarker and therapeutic target for CML.
Main Methods:
- CircRNA microarray analysis to identify differentially expressed circRNAs.
- Quantitative real-time PCR to verify hsa_circ_0058493 expression in PBMCs and exosomes.
- Functional assays (CCK8, flow cytometry, EdU) and gene silencing (shRNA) to assess biological functions.
Main Results:
- Hsa_circ_0058493 was significantly upregulated in CML patient PBMCs and associated with poor imatinib efficacy.
- Silencing hsa_circ_0058493 inhibited imatinib-resistant CML cell development.
- Hsa_circ_0058493 acts as a sponge for miR-548b-3p and is enriched in exosomes from resistant cells.
Conclusions:
- Hsa_circ_0058493 is a promising prognostic biomarker for CML.
- Hsa_circ_0058493 represents a potential therapeutic target for CML, particularly in imatinib-resistant cases.
- Exosomal hsa_circ_0058493 warrants further investigation for its role in CML progression and treatment response.
