miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements.
miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements.
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DOI：
10.1016/j.molcel.2009.08.020
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发表时间：
2009-09-11
期刊：
影响因子：
16
通讯作者：
Lieberman J
中科院分区：
文献类型：
--
作者：
Lal A;Navarro F;Maher CA;Maliszewski LE;Yan N;O'Day E;Chowdhury D;Dykxhoorn DM;Tsai P;Hofmann O;Becker KG;Gorospe M;Hide W;Lieberman J
miR-24在多个谱系的终末分化期间上调，抑制细胞周期进程。拮抗miR-24恢复有丝分裂后细胞增殖并增强成纤维细胞增殖，而过表达miR-24增加G1区室。在miR-24过表达后下调的248种mRNA高度富集DNA修复和细胞周期调控基因，这些基因与增强（MYC、E2 F2、CCNB 1、CDC 2）或抑制（p27 Kip 1、VHL）细胞周期进展的基因处的突出节点形成直接相互作用网络。miR-24直接调节MYC和E2 F2以及它们反式激活的一些基因。通过敲低E2 F2而不是MYC来消除拮抗miR-24所引起的增殖增强，并且通过miR-24不敏感的E2 F2来挽救由miR-24过表达抑制的细胞增殖。因此，E2 F2是关键的miR-24靶标。E2 F2 3′UTR缺少预测的miR-24识别元件。事实上，miR-24通过识别无籽但高度互补的序列来调节E2 F2、MYC、AURKB、CCNA 2、CDC 2、CDK 4和FEN 1的表达。
miR-24, up-regulated during terminal differentiation of multiple lineages, inhibits cell cycle progression. Antagonizing miR-24 restores post-mitotic cell proliferation and enhances fibroblast proliferation, while over-expressing miR-24 increases the G1 compartment. The 248 mRNAs down-regulated upon miR-24 over-expression are highly enriched for DNA repair and cell cycle regulatory genes that form a direct interaction network with prominent nodes at genes that enhance (MYC, E2F2, CCNB1, CDC2) or inhibit (p27Kip1, VHL) cell cycle progression. miR-24 directly regulates MYC and E2F2 and some genes they transactivate. Enhanced proliferation from antagonizing miR-24 is abrogated by knocking down E2F2, but not MYC, and cell proliferation, inhibited by miR-24 over-expression, is rescued by miR-24-insensitive E2F2. Therefore, E2F2 is a critical miR-24 target. The E2F2 3′UTR lacks a predicted miR-24 recognition element. In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4 and FEN1 by recognizing seedless, but highly complementary, sequences.
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