miR-497 and miR-34a retard lung cancer growth by co-inhibiting cyclin E1 (CCNE1).
miR-497 and miR-34a retard lung cancer growth by co-inhibiting cyclin E1 (CCNE1).
复制标题
miR-497 和 miR-34a 通过共同抑制细胞周期蛋白 E1 (CCNE1) 延缓肺癌生长
DOI：
10.18632/oncotarget.3693
复制
发表时间：
2015-05-30
期刊：
影响因子：
--
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Han Z;Zhang Y;Yang Q;Liu B;Wu J;Zhang Y;Yang C;Jiang Y
Cyclin E1 由 CCNE1 基因编码，促进 G1/S 转变、染色体不稳定和肿瘤发生。在这里，我们表明 miR-497 和 miR-34a 靶向 CCNE1 的 3'-UTR。 miR-497和miR-34a在癌细胞中下调，它们的异位表达抑制体外细胞增殖和集落形成，并抑制异种移植模型中的肿瘤生长。同时过表达miR-497和miR-34a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的下调作用均强于单独每种miRNA的作用。 miR-497 和 miR-34a 的协同作用与细胞周期蛋白 E1 水平部分相关。当稳定表达CCNE1的细胞用Hi-miR-497/34a质粒转染时，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，从而协同抑制人肺癌细胞的生长。
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.