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Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells

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Abstract

MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells. RNA pulldown coupled with proteomic analysis identified GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) as one of the RNA-binding proteins mediating GR-regulated miRNA maturation. Activated GR induced phosphorylation of v-AKT Murine Thymoma Viral Oncogene Homologue (AKT) kinase, which in turn phosphorylated and promoted nuclear translocation of G3BP1. The nuclear G3BP1 bound to the G3BP1 consensus sequence located on primary miR-15b~16-2 and miR-23a~27a~24-2 to inhibit their maturation. The findings from this study have advanced our understanding of the non-genomic effects of GR in the vascular system.

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Acknowledgements

We would like to thank Ms. Hoi Ki LEE for her preliminary work on this study.

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Authors and Affiliations

  1. Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China

    Hoi-Hin Kwok, Po-Ying Poon, Kylie Hin-Man Mak, Lin-Yao Zhang, Patrick Ying-Kit Yue & Ricky Ngok-Shun Wong

  2. Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China

    Pei Liu & Nai-Ki Mak

  3. Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia

    Huoming Zhang

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  1. Hoi-Hin Kwok
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  2. Po-Ying Poon
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  3. Kylie Hin-Man Mak
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  4. Lin-Yao Zhang
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  5. Pei Liu
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  6. Huoming Zhang
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  7. Nai-Ki Mak
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  9. Ricky Ngok-Shun Wong
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Correspondence to Ricky Ngok-Shun Wong.

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This work was supported by the Dr. Gilbert Hung Ginseng Laboratory Fund.

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The authors declare that they have no competing interests.

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Kwok, HH., Poon, PY., Mak, K.HM. et al. Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells. Cell. Mol. Life Sci. 74, 3613–3630 (2017). https://doi.org/10.1007/s00018-017-2540-y

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  • DOI: https://doi.org/10.1007/s00018-017-2540-y

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