title: Induction of differentiation-specific miRNAs in TPA-induced myeloid             leukemia cells through MEK/ERK activation.
abstract: Cellular microRNAs (miRNAs) are pivotal regulators involved in various biological             processes through the post-transcriptional regulation of gene expression. Signaling             pathways are extensively activated during 12-O-Tetradecanoylphorbol-13-acetate             (TPA)-induced differentiation of human leukemia cells, but the modulation of miRNA             expression and processing in this context has yet to be fully explored. In this             study, we comprehensively analyzed 10 miRNAs that are consistently upregulated             during TPA-induced differentiation of various leukemia cell lines by employing             microarray technology. The upregulation of these miRNAs was further verified by             quantitative RT-PCR, and, markedly, a subset of the miRNAs was found to be induced             via the MEK/ERK signaling pathway using TPA and specific pharmacological inhibitors.             Moreover, immunoblotting and quantitative RT-PCR analysis demonstrated that the             expression levels of key miRNA processing machineries (i.e., Drosha, Dicer, Ago1             and Ago2) were not induced in this context, but the transcription of the miRNA             products was triggered by MEK/ERK activation. Therefore, we identified the unique             miRNAs that respond to TPA treatment in leukemia cells and demonstrated the essential             role of the MEK/ERK signaling pathway in the induction of these miRNA transcripts.
authors.affiliation: Medical Systems Biology Research Center, School of Medicine, Tsinghua University, Beijing 100084, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.forename: Guangxin
authors.initials: G
authors.lastname: Xiang
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D010766:Phosphorylation; D012323:RNA Processing, Post-Transcriptional; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D035683:MicroRNAs; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate