LAUSR

BACKGROUND Multiple myeloma (MM) is a malignant tumor of plasma cells in the bone marrow. Circular RNAs (circRNAs) exert important activity in the tumorigenesis and chemoresistance of MM. In the current work, we sought to identify the expression, activity, and mechanism of circPSAP activity in MM. METHODS CircPSAP, microRNA (miR)-331-3p, and histone deacetylase 4 (HDAC4) were quantified by qRT-PCR and immunoblotting assays. Cell proliferation and survival were assessed by CCK-8 assay. Cell cycle and apoptosis were detected by flow cytometry. The direct relationship between miR-331-3p and circPSAP or HDAC4 3'UTR was validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. RESULTS CircPSAP was overexpressed in human MM and high levels of circPSAP predicted poor prognosis in MM patients. CircPSAP depletion repressed cell proliferation and promoted apoptosis and BTZ sensitivity. Mechanistically, circPSAP functioned as a miR-331-3p sponge, and circPSAP regulated cell proliferation, apoptosis and BTZ sensitivity by sponging miR-331-3p. MiR-331-3p directly targeted and inhibited HDAC4. MiR-331-3p-mediated inhibition of HDAC4 impaired cell proliferation and enhanced cell apoptosis and BTZ sensitivity. Moreover, circPSAP modulated HDAC4 expression by acting as a miR-331-3p sponge. CONCLUSION Our findings highlight a novel mechanism, in which circPSAP functions as a miR-331-3p sponge to impact MM cell proliferation, apoptosis and BTZ sensitivity by regulating HDAC4 expression.