Dysregulated circular RNAs are closely linked to multiple myeloma prognosis, with circ_0026652 predicting bortezomib-based treatment response and survival via the microRNA-608-mediated Wnt/beta-catenin pathway

Circular RNA (circRNA/circ) profiles have been suggested to be involved in the prognosis of several types of solid tumors and hematological malignancies, including multiple myeloma (MM). Therefore, the aim of the present study was to comprehensively explore the involvement of circRNA profiles in MM prognosis. A total of 60 patients with MM that underwent bortezomib-based induction therapy were enrolled. Next, eight patients with complete response (CR) and eight with no response (NR) were randomly selected to detect their circRNA profiles in bone marrow plasma cells (BMPCs) by microarray. Next, 10 candidate circRNAs were verified via reverse transcription-quantitative PCR (RT-qPCR) in the BMPCs of 60 patients with MM. Finally, the molecular mechanism of circ_0026652 knockdown underlying the regulation of chemosensitivity to bortezomib was assessed. Microarray showed that 79 circRNAs were upregulated and 167 were downregulated in CR compared with NR cases, which were found to be enriched in carcinogenic and chemoresistance-related pathways (Wnt, mTOR and MAPK pathways). RT-qPCR showed that 8/10 circRNAs (circ_0026652, circ_0068708, circ_0088128, circ_0001566, circ_0031113, circ_0083587, circ_0005552 and circ_0007171) were associated with treatment response [CR or objective response rate (ORR)] and 5/10 circRNAs (circ_0026652, circ_0068708, circ_0001566, circ_0031113 and circ_0005552) were associated with progression-free survival (PFS) or overall survival (OS). Of note, circ_0026652 was a key prognostic marker simultaneously associated with CR, ORR, PFS and OS. Cellular experiments showed that circ_0026652 knockdown enhanced chemosensitivity to bortezomib through the microRNA (miR)-608-mediated Wnt/beta-catenin pathway in U266 and RPIM-8226 cells. In conclusion, dysregulated circRNA profiles were closely associated with MM prognosis, with circ_0026652 being linked to bortezomib-based treatment response and survival through the miR-608-mediated Wnt/beta-catenin pathway.