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

An-Ni Zhong; Yi Yin; Bing-Jie Tang; Lei Chen; Hong-Wei Shen; Zhi-Ping Tan; Wen-Qun Li; Qun He; Bao Sun; Yan Zhu; Jie Xiao; Zhi-Ping Jiang; Ping Xu

doi:10.3389/fphar.2021.728916

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

Front Pharmacol. 2021 Sep 13:12:728916. doi: 10.3389/fphar.2021.728916. eCollection 2021.

Authors

An-Ni Zhong^{1

2

3}, Yi Yin^{1

2}, Bing-Jie Tang^{1

2}, Lei Chen^{1

2}, Hong-Wei Shen⁴, Zhi-Ping Tan⁵, Wen-Qun Li^{1

2}, Qun He⁶, Bao Sun^{1

2}, Yan Zhu^{1

2

7}, Jie Xiao^{1

2}, Zhi-Ping Jiang⁶, Ping Xu^{1

2}

Affiliations

¹ Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.
² Institute of Clinical Pharmacy, Central South University, Changsha, China.
³ Department of Pharmacy, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁴ Medical Experiment Research Centre, The Second Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
⁶ Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.
⁷ Department of Pharmacy, Affiliated Hospital of Zunyi Medical University, Zunyi, 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.

Keywords: chronic myelogenous leukemia; drug resistance; exosome; hsa_circ_0058493; imatinib.