Circ_0007841 promotes the progression of multiple myeloma via miR-338-3p/BRD4 axis

Abstract

Background The pathogenesis of multiple myeloma (MM) is not completely known. Herein, we explored the function and the working mechanism of circular RNA circ_0007841 in MM progression. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of circ_0007841, microRNA-338-3p (miR-338-3p) and bromodomain containing 4 (BRD4). The proliferation and metastasis of MM cells were examined by cell counting kit-8 (CCK8) assay and transwell assays. Flow cytometry was conducted to assess the cell cycle and the apoptosis of MM cells. The targets of circ_0007841 and miR-338-3p were predicted by circinteractome and targetscan softwares, and these predictions were confirmed by dual-luciferase reporter assay and RNA-pull down assay. The protein levels of BRD4, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), PI3K, p-AKT serine/threonine kinase (p-AKT) and AKT were measured by Western blot assay. Exosomes were extracted using Exosome isolation kit. Results Circ_0007841 was highly expressed in bone marrow (BM)-derived plasma cells of MM patients and MM cells than that in healthy volunteers and normal plasma cells nPCs. Circ_0007841 promoted the proliferation, cell cycle and metastasis and impeded the apoptosis of MM cells. MiR-338-3p was a direct target of circ_0007841 in MM cells. Circ_0007841 accelerated the progression of MM through targeting miR-338-3p. BRD4 could directly bind to miR-338-3p in MM cells. MiR-338-3p exerted an anti-tumor role through targeting BRD4. Circ_0007841 promoted the activation of PI3K/AKT signaling via miR-338-3p/BRD4 axis. Exosomes generated from mesenchymal stromal cells (MSCs) elevated the malignant behaviors of MM cells via circ_0007841. Conclusion Circ_0007841 acted as an oncogene to promote the proliferation, cell cycle and motility and restrain the apoptosis of MM cells through sequestering miR-338-3p to up-regulate the expression of BRD4.