Han Zhiyuan, Zhang Yanbin, Yang Qiaoyuan, Liu Binbin, Wu Jianjun, Zhang Yajie, Yang Chengfeng, Jiang Yiguo
State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, P.R. China.
Department of Pulmonary Tuberculosis, Guangzhou Chest Hospital, Guangzhou, P.R. China.
Oncotarget. 2015 May 30;6(15):13149-63. doi: 10.18632/oncotarget.3693.
Cyclin E1, encoded by the CCNE1 gene, promotes G1/S transition, chromosome instability, and oncogenesis. Here, we show that miR-497 and miR-34a target the 3'-UTR of CCNE1. miR-497 and miR-34a are downregulated in cancer cells and their ectopic expression inhibited cell proliferation and colony formation in vitro, and inhibited tumor growth in a xenograft model. The effect of simultaneous overexpression of miR-497 and miR-34a on the inhibition of cell proliferation, colony formation, and tumor growth, and the downregulation of cyclin E1 was stronger than the effect of each miRNA alone. The synergistic actions of miR-497 and miR-34a partly correlated with cyclin E1 levels. When cells stably expressing CCNE1 were transfected with the Hi-miR-497/34a plasmid, there was no effect on colony formation, compared with that of cells transfected with either Hi-miR497 or Hi-miR34a. These results indicate cyclin E1 is downregulated by both miR-497 and miR-34a, which synergistically retard the growth of human lung cancer cells.
由CCNE1基因编码的细胞周期蛋白E1促进G1/S期转换、染色体不稳定和肿瘤发生。在此，我们表明miR-497和miR-34a靶向CCNE1的3'-UTR。miR-497和miR-34a在癌细胞中表达下调，其异位表达在体外抑制细胞增殖和集落形成，并在异种移植模型中抑制肿瘤生长。miR-497和miR-34a同时过表达对细胞增殖、集落形成和肿瘤生长的抑制作用以及细胞周期蛋白E1的下调作用比单独使用每种miRNA的作用更强。miR-497和miR-34a的协同作用部分与细胞周期蛋白E1水平相关。当用Hi-miR-497/34a质粒转染稳定表达CCNE1的细胞时，与用Hi-miR497或Hi-miR34a转染的细胞相比，对集落形成没有影响。这些结果表明细胞周期蛋白E1被miR-497和miR-34a下调，二者协同抑制人肺癌细胞的生长。
