title: 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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo 315211, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Pan
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Gong
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhong
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Dong
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.forename: Yanping
authors.initials: Y
authors.lastname: Le
authors.forename: Junming
authors.initials: J
authors.lastname: Guo
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: C000715187:Lin28A protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases