Circ_0005615 restrains the progression of multiple myeloma through modulating miR-331-3p and IGF1R regulatory cascade
Journal of Orthopaedic Surgery and Research(2023)
Abstract
Abstract Background Circular RNAs are implicated in modulating the progression of various malignant tumors. However, the function and underlying mechanisms of circ_0005615 in multiple myeloma (MM) remain unclear. Methods The expression levels of circ_0005615, miR-331-3p and IGF1R were tested by quantitative real-time polymerase chain reaction or western blot assay. Cell counting kit-8 and 5-ethynyl-2′-deoxyuridine (EdU) assay were performed for cell proliferation detection. Cell apoptosis and cell cycle were measured by flow cytometry. The protein expressions of Bax and Bcl-2 were detected by western blot assay. Glucose consumption, lactate production and ATP/ADP ratios were estimated to disclose cell glycolysis. The interaction relationship among miR-331-3p and circ_0005615 or IGF1R was proved by dual-luciferase reporter assay. Results The abundance of circ_0005615 and IGF1R was increased in MM patients and cells, while the expression of miR-331-3p was decreased. Circ_0005615 inhibition retarded the proliferation and cell cycle progression, while reinforced the apoptosis of MM cells. Molecularly, circ_0005615 could sponge miR-331-3p, and the repressive trends of circ_0005615 deficiency on MM progression could be alleviated by anti-miR-331-3p introduction. Additionally, IGF1R was validated to be targeted by miR-331-3p, and IGF1R overexpression mitigated the suppressive function of miR-331-3p on MM development. Furthermore, IGF1R was mediated by circ_0005615/miR-331-3p axis in MM cells. Conclusion Circ_0005615 downregulation blocked MM development by targeting miR-331-3p/IGF1R axis.
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