CircRERE confers the resistance of multiple myeloma to bortezomib depending on the regulation of CD47 by exerting the sponge effect on miR-152-3p

Wei Fang; Jiao Mu; Yi Yang; Lin Liu

doi:10.1016/j.jbo.2021.100381

CircRERE confers the resistance of multiple myeloma to bortezomib depending on the regulation of CD47 by exerting the sponge effect on miR-152-3p

J Bone Oncol. 2021 Jul 8:30:100381. doi: 10.1016/j.jbo.2021.100381. eCollection 2021 Oct.

Authors

Wei Fang^{1

2}, Jiao Mu¹, Yi Yang², Lin Liu¹

Affiliations

¹ Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing City 400016, China.
² Department of Hematology, Chongqing University Three Gorges Hospital, Chongqing City 404100, China.

Abstract

Background: Inevitable resistance to chemotherapeutic drugs has become a major obstacle for the clinical treatment of multiple myeloma (MM). Circular RNAs (circRNAs) can regulate the chemoresistance in different tumors. Our study was to explore the regulation of circRNA arginine-glutamic acid dipeptide repeats (circRERE) in bortezomib (BTZ) resistance of MM.

Methods: CircRERE, microRNA-152-3p (miR-152-3p) and cluster of differentiation 47 (CD47) levels were assayed through the quantitative real-time polymerase chain reaction (qRT-PCR). Cell sensitivity to BTZ was analyzed using Cell Counting Kit-8 (CCK-8) assay. Cell proliferation and apoptosis were determined via colony formation assay and flow cytometry, respectively. The detection of all proteins was conducted by western blot. The target binding was analyzed via the dual-luciferase reporter assay and RIP assay.

Results: We found the upregulation of circRERE in BTZ-resistant MM samples and cells. BTZ resistance was inhibited after circRERE expression was downregulated in MM cells. CircRERE was identified to act as a miR-152-3p sponge. The effect of circRERE on the BTZ resistance was associated with the sponge function for miR-152-3p. CD47 was a target for miR-152-3p and circRERE could sponge miR-152-3p to generate the expression regulation of CD47. MiR-152-3p facilitated the susceptibility of MM cells to BTZ by targeting CD47.

Conclusion: These results suggested that circRERE could suppress the BTZ resistance in MM cells by mediating the miR-152-3p/CD47 axis.

Keywords: Bortezomib; CD47; CircRERE; Multiple myeloma; miR-152-3p.