TAILIEUCHUNG - Báo cáo khoa học: Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by inhibiting translation and⁄or inducing degradation of target mRNAs, and they play important roles in a wide variety of biological func-tions including cell differentiation, tumorigenesis, apoptosis and metabo-lism. | Sustained activation of ERK1 2 by NGF induces microRNA-221 and 222 in PC12 cells Kazuya Terasawa1 Atsuhiko Ichimura1 Fumiaki Sato2 Kazuharu Shimizu2 and Gozoh Tsujimoto1 1 Department of Pharmcogenomics Graduate Schoolof PharmaceuticalSciences Kyoto University Sakyo-ku Japan 2 Department of Nanobio Drug Discovery Graduate Schoolof PharmaceuticalSciences Kyoto University Sakyo-ku Japan Keywords Bim ERK1 2 microRNA NGF PC12 Correspondence G. Tsujimoto 45-29 Yoshida-Shimo-Adachi-cho Sakyo-ku Kyoto 606-8501 Japan Fax 81 75 753 4523 Tel 81 75 753 4544 E-mail gtsuji@ Received 18 December 2008 revised 13 March 2009 accepted 6 April 2009 doi MicroRNAs miRNAs are small non-coding RNAs that regulate gene expression by inhibiting translation and or inducing degradation of target mRNAs and they play important roles in a wide variety of biological functions including cell differentiation tumorigenesis apoptosis and metabolism. However there is a paucity of information concerning the regulatory mechanism of miRNA expression. Here we report identification of growth factor-regulated miRNAs using the PC12 cell line an established model of neuronal growth and differentiation. We found that expression of miR-221 and miR-222 expression were induced by nerve growth factor NGF stimulation in PC12 cells and that this induction was dependent on sustained activation of the extracellular signal-regulated kinase 1 and 2 ERK1 2 pathway. Using a target prediction program we also identified a pro-apo-totic factor the BH3-only protein Bim as a potential target of miR-221 222. Overexpression of miR-221 or miR-222 suppressed the activity of a luciferase reporter activity fused to the 3 UTR of Bim mRNA. Furthermore overexpression of miR-221 222 decreased endogenous Bim mRNA expression. These results reveal that the ERK signal regulates miR-221 222 expression and that these miRNAs might contribute to NGF-dependent cell survival in PC12 cells. .

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