Lin-28 reactivation is required for let-7 repression and proliferation in human small cell lung cancer cells
Lin-28 reactivation is required for let-7 repression and proliferation in human small cell lung cancer cells
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DOI：
10.1007/s11010-011-0862-x
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发表时间：
2011-09-01
影响因子：
4.3
通讯作者：
Guo, Junming
中科院分区：
文献类型：
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作者：
Pan, Lin;Gong, Zhaohui;Guo, Junming
已知let-7 microRNAs家族（miRNAs）在肺癌中起肿瘤抑制作用并下调。最近，rna结合蛋白Lin-28被证明通过阻断Drosha和dicer介导的裂解和加速let-7前体的衰变来抑制let-7 mirna的生物发生。我们选取NCI-H446肺小细胞肺癌细胞，以确定Lin-28通过负调控let-7生物发生促进细胞增殖、影响细胞周期是否具有广泛代表性。在这里，我们发现lin - 28mrna在高c-Myc状态的NCI-H446细胞中上调。real-time RT-PCR结果进一步表明，pri-let-7a-1/7g和成熟let-7g显著下调。lin-28的表达下调，而成熟的let-7g转录本的表达则相反上调。MTT实验表明，lin-28抑制的肺癌细胞增殖明显受损。lin-28敲低的细胞G1/G0期细胞比例较高，S期细胞比例较低。结果表明，Lin-28的诱导可以介导let-7家族成员的抑制，促进细胞周期进程，抑制细胞增殖。
The let-7 family of microRNAs (miRNAs) are known to act as tumor suppressors and down-regulated in lung cancer. Recently, the RNA-binding protein Lin-28 was demonstrated to inhibit biogenesis of let-7 miRNAs by blocking both Drosha- and Dicer-mediated cleavage and accelerating decay of let-7 precursors. We selected NCI-H446 lung small cell lung cancer cell to determine whether it is broadly representative that Lin-28 can promote cell proliferation and affect cell cycle through negatively regulating let-7 biogenesis. Here, we showed that Lin-28 mRNA was up-regulated in NCI-H446 cell with a high c-Myc state. The result of real-time RT-PCR further indicated that pri-let-7a-1/7g and mature let-7g were remarkably down-regulated. The expression of lin-28 was down-regulated while the mature let-7g transcript was up-regulated inversely. The MTT assay indicated that the proliferation of lung cancer cells with lin-28 inhibition was signally impaired. The cells with lin-28 knockdown revealed a higher proportion of cells at G1/G0 phase and less at S phase. The results presented here demonstrate that induction of Lin-28 could mediate repression of let-7 family members, promote cell cycle progression and suppress cell proliferation.