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Lin-28 reactivation is required for let-7 repression and proliferation in human small cell lung cancer cells

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Abstract

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.

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Acknowledgments

This study was supported in part by research grants from the Natural Science Foundation of Ningbo (2009A610187), the Social Development Program of Ningbo (2007C10016), the Excellent Young Teachers Program of Education of Zhejiang Province, the K.C. Wong Magna Fund and Excellent Master Dissertation Cultivation Fund at Ningbo University.

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  1. Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, 315211, China

    Lin Pan, Zhaohui Gong, Zhiwei Zhong, Zhuo Dong, Qiong Liu, Yanping Le & Junming Guo

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  1. Lin Pan
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  2. Zhaohui Gong
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  3. Zhiwei Zhong
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  4. Zhuo Dong
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  6. Yanping Le
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  7. Junming Guo
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Correspondence to Zhaohui Gong.

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Pan, L., Gong, Z., Zhong, Z. et al. Lin-28 reactivation is required for let-7 repression and proliferation in human small cell lung cancer cells. Mol Cell Biochem 355, 257–263 (2011). https://doi.org/10.1007/s11010-011-0862-x

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  • DOI: https://doi.org/10.1007/s11010-011-0862-x

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