RESUMO
Leukemia is a group of life-threatening hematological malignancies which is currently incurable and often accompanied by drug resistance or disease relapse. Understanding the pathogenesis of leukemia and finding specific therapeutic targets and biomarkers is of great importance to improve the clinical efficacy of leukemia. Exosome-derived ncRNAs have been demonstrated as critical components of intercellular communication and function as key facilitators in the leukemia biological process. This review outlines the current investigations of exosomal ncRNAs (including miRNA, circRNA, and lncRNA) as important mediators of leukemia and potential therapeutic targets and biomarkers for leukemia treatment. Moreover, we generally analyze the prospects and challenges for exosomal ncRNAs from the aspects of research and clinical application.
RESUMO
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.