环状RNA RERE通过对miR-152-3p发挥海绵效应，依赖于对CD47的调控，赋予多发性骨髓瘤对硼替佐米的抗性。

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

作者信息

Fang Wei, Mu Jiao, Yang Yi, Liu Lin

机构信息

Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing City 400016, China.

Department of Hematology, Chongqing University Three Gorges Hospital, Chongqing City 404100, China.

出版信息

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

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.

背景

化疗药物不可避免的耐药性已成为多发性骨髓瘤（MM）临床治疗的主要障碍。环状RNA（circRNA）可调节不同肿瘤中的化疗耐药性。我们的研究旨在探讨环状RNA精氨酸 - 谷氨酸二肽重复序列（circRERE）在MM硼替佐米（BTZ）耐药中的调节作用。

方法

通过定量实时聚合酶链反应（qRT-PCR）检测circRERE、微小RNA-152-3p（miR-152-3p）和分化簇47（CD47）水平。使用细胞计数试剂盒-8（CCK-8）检测分析细胞对BTZ的敏感性。分别通过集落形成试验和流式细胞术测定细胞增殖和凋亡。所有蛋白质的检测均通过蛋白质免疫印迹法进行。通过双荧光素酶报告基因检测和RNA免疫沉淀试验分析靶标结合情况。

结果

我们发现circRERE在BTZ耐药的MM样本和细胞中上调。在MM细胞中下调circRERE表达后，BTZ耐药性受到抑制。circRERE被鉴定为miR-152-3p的海绵。circRERE对BTZ耐药性的影响与对miR-152-3p的海绵功能有关。CD47是miR-152-3p的靶标，circRERE可以海绵化miR-152-3p以产生对CD47的表达调控。miR-152-3p通过靶向CD47促进MM细胞对BTZ的敏感性。