Circ_0005615 restrains the progression of multiple myeloma through modulating miR-331-3p and IGF1R regulatory cascade

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.