title: MicroRNA-155 Downregulation Promotes Cell Cycle Arrest and Apoptosis in Diffuse Large B-Cell Lymphoma.
abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma in the adult population, and treatment of DLBCL is still unfavorable. Therefore, there is an urgent requirement to investigate the molecular mechanisms underlying DLBCL tumorigenesis. To study the potential function of microRNA-155 (miR-155) involved in the regulation of lymphoma, we monitored lymphoma cell behavior including proliferation, cell cycle, and apoptosis using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the expression levels of miR-155 in 118 lymphoma patients' tissues, and Western blot was also used to analyze the expression level of proteins correlated with cell cycle and apoptosis in lymphoma cells. miR-155 expression levels were higher in lymphoma tissues compared with adjacent tissues. Downregulation of miR-155 inhibited lymphoma cell progress by arresting cell cycle in the G0/G1 phase and promoting apoptosis. Cell cycle-correlated proteins (cyclin B1, cyclin D1, and CDK4) were inhibited by downregulation of miR-155. Apoptosis-correlated proteins level (Bax/Bcl-2 and caspase 3 activity) were increased by downregulation of miR-155. In addition, a significant inverse correlation between the level of miR-155 and transforming growth factor-β receptor 2 (TGFBR2) was observed, which has been demonstrated to be a novel tumor suppressor gene. A further in vivo tumor formation study in nude mice indicated that downregulation of miR-155 in lymphoma cells delayed the progress of tumor formation. These findings indicate that miR-155 may serve as a useful potential target for the treatment of lymphoma.
authors.affiliation: Department of Pathology, the Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, P.R. China.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.forename: Na
authors.initials: N
authors.lastname: Tang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Tang
authors.forename: Bo-Ping
authors.initials: BP
authors.lastname: Zhou
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Li
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Wu
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Zeng
authors.forename: Shu-Song
authors.initials: SS
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D016192:Resting Phase, Cell Cycle / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs