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

Yan Wang, Quande Lin, Chunge Song, Ruojin Ma, Xiaojie Li
2020 unpublished
Background: The pathogenesis of multiple myeloma (MM) is not completely known. Finding novel targets are urgently needed for MM treatment. 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
more » ... ere 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.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.
doi:10.21203/rs.3.rs-17503/v2 fatcat:kwwxbxhd5fgfrmob6t3jcvdtna