Hsa_circ_0000877 facilitates the progression of diffuse large B-cell lymphoma by miR-370-3p/mitogen-activated protein kinase kinase kinase kinase 4/Hippo pathway

Diffuse large B-cell lymphoma (DLBCL) originates from B lymphocytes and is a fatal hematological malignancy. Circular RNAs have been increasingly reported as a promising biological target for cancer therapy, but their role in DLBCL remains poorly studied. Relative expression levels of has_circ_0000877 (circ_0000877), microRNA-370-3p (miR-370-3p), and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) were assessed by quantitative real-time PCR. Western blot analysis was employed to measure protein levels. Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect the proliferation of TMD8 and U2932 cells. Cell cycle and apoptosis were investigated by flow cytometry. Transwell assay was used to analyze cell migration and invasion. Molecular interaction was determined by dual-luciferase reporter assay and RNA immunoprecipitation assay. The protein expression of Ki67 in tumor tissues of mice was detected by immunohistochemistry assay. The expression of circ_0000877 was markedly elevated in DLBCL tissues and cell lines. The decreased expression of circ_0000877 significantly inhibited proliferation, migration, and invasion of DLBCL cell lines. In addition, silencing circ_0000877 promoted cell apoptosis and induced cell cycle arrest in G0/G1 phase. Then, miR-370-3p directly interacted with circ_0000877 and MAP4K4. Circ_0000877 promoted MAP4K4 level by sponging miR-370-3p. MAP4K4 depletion inhibited the activation of Hippo pathway. Finally, circ_0000877 silencing significantly prevented the growth of DLBCL cells in vivo . Our findings revealed that circ_0000877 could regulate the malignant evolution of DLBCL by miR-370-3p/MAP4K4/Hippo pathway.