title: miR-9 enhances the transactivation of nuclear factor of activated T cells by targeting KPNB1 and DYRK1B.
abstract: The fast response to stimuli and subsequent activation of the nuclear factor of activated T cells (NFAT) signaling pathway play an essential role in human T cell functions. MicroRNAs (miRNAs) are increasingly implicated in regulation of numerous biological and pathological processes. In this study we demonstrate a novel function of miRNA-9 (miR-9) in regulation of the NFAT signaling pathway. Upon PMA-ionomycin stimulation, miR-9 was markedly increased, consistent with NFAT activation. Overexpression of miR-9 significantly enhanced NFAT activity and accelerated NFAT dephosphorylation and its nuclear translocation in response to PMA-ionomycin. Karyopherin-β1 (KPNB1, a nucleocytoplasmic transporter) and dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) were identified as direct targets of miR-9. Functionally, miR-9 promoted IL-2 production in stimulated human lymphocyte Jurkat T cells. Collectively, our data reveal a novel role for miR-9 in regulation of the NFAT pathway by targeting KPNB1 and DYRK1B.
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, China; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, China;
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, China;
authors.forename: Yuna
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, China;
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, China;
authors.forename: Kang
authors.initials: K
authors.lastname: Kang
authors.affiliation: Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, China;
authors.forename: Xiao
authors.initials: X
authors.lastname: Peng
authors.affiliation: Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, China;
authors.forename: Wenda
authors.initials: W
authors.lastname: Peng
authors.affiliation: Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, China;
authors.forename: Junle
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma; and.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: J Usha
authors.initials: JU
authors.lastname: Raj
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, China; dmgou@szu.edu.cn.
authors.forename: Deming
authors.initials: D
authors.lastname: Gou
mesh_terms: D021581:Active Transport, Cell Nucleus; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism*; D000097603:Dyrk Kinases
chemical_list: D007376:Interleukin-2; D015759:Ionomycin; D035683:MicroRNAs; D050778:NFATC Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate; D028961:beta Karyopherins; D000097603:Dyrk Kinases; C508594:IL2 protein, human; C424166:KPNB1 protein, human; C541874:MIRN92 microRNA, human
keywords: IL-2; Jurkat T cells; NFAT; miR-9