Long non-coding RNA H19 promotes tumorigenesis of multiple myeloma by activating BRD4 signaling by targeting miR-152-3p.

Multiple myeloma (MM) accounts for over twenty percent of hematological cancer-related death worldwide. Long non-coding RNA (lncRNA) H19 is associated with multiple tumorigenesis and is increased in MM, but the underlying mechanism of H19 in MM is unclear. In this study, the expression of H19, miR-152-3p and BRD4 in MM patients was evaluated by qRT-PCR and Western blotting. Colony formation and flow cytometry analysis were used to determine the effects of H19 and miR-152-3p on MM cell proliferation, apoptosis and cell cycle. Luciferase reporter assay was conducted to confirm the interaction among H19, miR-152-3p and BRD4. Nude mice xenograft model was established, and the cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) staining and TUNEL assay. We found that levels of H19 and BRD4 were up-regulated, and the expression of miR-152-3p was down-regulated in MM patients. Dual luciferase reporter assay showed H19 targeted miR-152-3p to promote BRD4 expression. Knockdown of H19 repressed proliferation, and enhanced apoptosis and cell cycle G1 arrest by up-regulating miR-152-3p in MM cells. Furthermore, H19 knockdown suppressed the growth of xenograft tumor, and reduced Ki-67 and BRD4 level, as well as increased cell apoptosis in xenograft tumor tissues. Taken together, H19 knockdown suppresses MM tumorigenesis via inhibiting BRD4-mediated cell proliferation through targeting miR-152-3p, implying that H19 may be a promising biomarker and drug target for MM. [ABSTRACT FROM AUTHOR]