Inhibition of hsa_circ_0003489 shifts balance from autophagy to apoptosis and sensitizes multiple myeloma cells to Bortezomib via miR-874-3p/HDAC1 axis.

Background Circular RNAs (circRNAs) crucially regulate tumor progression. In this study, we examined the functional roles and mechanisms of hsa_circ_0003489 in multiple myeloma (MM). Methods Upon altering the expressions of hsa_circ_0003489, miR-874-3p, and/or histone deacetylase 1 (HDAC1) in MM1.R cells and treating them with Bortezomib (BTZ), cell viability was examined by CCK-8 assay, cell proliferation by Ki-67 immunofluorescence, apoptosis by TUNEL staining, flow cytometry and western blot, autophagy by electron microscopy and western blot. The interaction between hsa_circ_0003489 and miR-874-3p as well as that between miR-874-3p and HDAC1 were examined by expressional analysis, dual luciferase reporter assay, and RNA immunoprecipitation. The in vivo impacts of hsa_circ_0003489 on MM growth and sensitivity to BTZ were examined using an MM xenograft mouse model. Results Knocking down hsa_circ_0003489 significantly inhibited the viability, cell proliferation, and the autophagy, while promoted the apoptosis of MM cells in vitro and MM xenograft in vivo. Suppressing hsa_circ_0003489 also further boosted the cytotoxic effects of BTZ in MM cells and reversed its promoting effect on autophagy. Mechanically, hsa_circ_0003489 acted as a sponge of miR-874-3p and positively regulated the expression of miR-874-3p target, HDAC1. MiR-874-3p and HDAC1 essentially mediated the effects of hsa_circ_0003489 on cell viability, proliferation, apoptosis, and autophagy. Conclusion The hsa_circ_0003489/miR-874-3p/HDAC1 axis critically regulates the balance between apoptosis and autophagy. Silencing hsa_circ_0003489 sensitizes MM cells to BTZ by prohibiting autophagy and thus may boost the therapeutic effects of BTZ.