Regulation of Corticosteroidogenic Genes by MicroRNAs
The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2017/2021903 |
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| author | Stacy Robertson Louise A. Diver Samantha Alvarez-Madrazo Craig Livie Ayesha Ejaz Robert Fraser John M. Connell Scott M. MacKenzie Eleanor Davies |
| author_facet | Stacy Robertson Louise A. Diver Samantha Alvarez-Madrazo Craig Livie Ayesha Ejaz Robert Fraser John M. Connell Scott M. MacKenzie Eleanor Davies |
| author_sort | Stacy Robertson |
| collection | DOAJ |
| description | The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Bioinformatic analysis of genes involved in corticosteroid biosynthesis or metabolism identified many putative microRNA-binding sites, and some were selected for further study. Manipulation of individual microRNA levels demonstrated a direct effect of miR-125a-5p and miR-125b-5p on CYP11B2 and of miR-320a-3p levels on CYP11A1 and CYP17A1 mRNA. Finally, comparison of microRNA expression profiles from human aldosterone-producing adenoma and normal adrenal tissue showed levels of various microRNAs, including miR-125a-5p to be significantly different. This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature. |
| format | Article |
| id | doaj-art-07845c815a2f46d7a82918b5cc307ca5 |
| institution | OA Journals |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-07845c815a2f46d7a82918b5cc307ca52025-08-20T02:02:50ZengWileyInternational Journal of Endocrinology1687-83371687-83452017-01-01201710.1155/2017/20219032021903Regulation of Corticosteroidogenic Genes by MicroRNAsStacy Robertson0Louise A. Diver1Samantha Alvarez-Madrazo2Craig Livie3Ayesha Ejaz4Robert Fraser5John M. Connell6Scott M. MacKenzie7Eleanor Davies8Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UKInstitute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UKInstitute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UKInstitute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UKInstitute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UKInstitute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UKNinewells Hospital and Medical School, University of Dundee, Dundee, UKInstitute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UKInstitute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UKThe loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Bioinformatic analysis of genes involved in corticosteroid biosynthesis or metabolism identified many putative microRNA-binding sites, and some were selected for further study. Manipulation of individual microRNA levels demonstrated a direct effect of miR-125a-5p and miR-125b-5p on CYP11B2 and of miR-320a-3p levels on CYP11A1 and CYP17A1 mRNA. Finally, comparison of microRNA expression profiles from human aldosterone-producing adenoma and normal adrenal tissue showed levels of various microRNAs, including miR-125a-5p to be significantly different. This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature.http://dx.doi.org/10.1155/2017/2021903 |
| spellingShingle | Stacy Robertson Louise A. Diver Samantha Alvarez-Madrazo Craig Livie Ayesha Ejaz Robert Fraser John M. Connell Scott M. MacKenzie Eleanor Davies Regulation of Corticosteroidogenic Genes by MicroRNAs International Journal of Endocrinology |
| title | Regulation of Corticosteroidogenic Genes by MicroRNAs |
| title_full | Regulation of Corticosteroidogenic Genes by MicroRNAs |
| title_fullStr | Regulation of Corticosteroidogenic Genes by MicroRNAs |
| title_full_unstemmed | Regulation of Corticosteroidogenic Genes by MicroRNAs |
| title_short | Regulation of Corticosteroidogenic Genes by MicroRNAs |
| title_sort | regulation of corticosteroidogenic genes by micrornas |
| url | http://dx.doi.org/10.1155/2017/2021903 |
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