CircRNA Microarray Profiling Reveals hsa_circ_0058493 as a Novel Biomarker for Imatinib-Resistant CML

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.

Comprehensive elaboration of circular RNA in multiple myeloma

“…To date, increasing literature demonstrates that circRNAs play a crucial role in the pathology of various diseases, including neuronal diseases ( Kumar et al, 2018 ; Dube et al, 2019 ), diabetes ( Liu et al, 2019 ) and cancer ( Guarnerio et al, 2016b ; Tang et al, 2021 ). Particularly, circRNAs serve important functions in hematological malignancies ( Bonizzato et al, 2016 ; Dahl et al, 2018 ), and our group also reveals that circRNAs can be a promising prognostic biomarker in hematological malignancies ( Zhong et al, 2021 ). Furthermore, circRNAs have also been found to be critically involved in cancer initiation, development and drug resistance ( Guarnerio et al, 2016a ; Borran et al, 2020 ).…”

The Landscape of Exosome-Derived Non-Coding RNA in Leukemia

“… Bi et al (2021) found that oncogene circ_0004136 could promote AML development through regulating miR-570-3p/TSPAN3 axis while exosome-mediated circ_0004136 knockdown restrained AML cell malignant progression. Our recent study also demonstrated that upregulated circ_0058493 in exosomes derived from CML cells was associated with imatinib resistance ( Zhong et al, 2021 ). Besides, Wu et al (2020) identified a novel mitochondrial genome-derived circRNAs (Mc), mc-COX2.…”

Emerging roles of circRNAs in leukemia and the clinical prospects: An update

“… 40 Circ_0058493 was significantly overexpressed in PBMCs of CML patients with poor clinical response to imatinib. 41 Knockdown of circ_0058493 markedly repressed the growth of imatinib‐resistant CML cells probably via acting as a molecular sponge to miR‐548b‐3p, suggesting that circ_0058493 in PBMCs might be a useful prognostic biomarker as well as a therapeutic target for CML. 41 CircHIPK3 was also significantly elevated in PBMCs and the serum in CML patients with poor outcomes.…”