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

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.