MicroRNA-155 Downregulation Promotes Cell Cycle Arrest and Apoptosis in Diffuse Large B-Cell Lymphoma

细胞周期 下调和上调 癌症研究 细胞周期蛋白D1 和平号-155 淋巴瘤 细胞凋亡 生物 癌变 细胞周期检查点 弥漫性大B细胞淋巴瘤 小RNA 细胞生长 细胞周期蛋白D3 免疫学 癌症 基因 生物化学 遗传学
作者
Fuqiang Zhu,Li Zeng,Na Tang,Ya‐Ping Tang,Boping Zhou,Fangfang Li,Weigang Wu,Xiaobing Zeng,Shusong Peng
出处
期刊:Oncology Research [Cognizant, LLC]
卷期号:24 (6): 415-427 被引量:42
标识
DOI:10.3727/096504016x14685034103473
摘要

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 G 0 /G 1 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.
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