Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAs
Glucocorticoids (GCs) are pleiotropic hormones which regulate innumerable physiological processes. Their comprehensive effects are due to the diversity of signaling mechanism networks. MiRNAs, small, non-coding RNAs contribute to the fine tuning of signaling pathways and reciprocal regulation betwee...
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11778 |
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| author | Henriett Butz Katalin Mészáros István Likó Attila Patocs |
| author_facet | Henriett Butz Katalin Mészáros István Likó Attila Patocs |
| author_sort | Henriett Butz |
| collection | DOAJ |
| description | Glucocorticoids (GCs) are pleiotropic hormones which regulate innumerable physiological processes. Their comprehensive effects are due to the diversity of signaling mechanism networks. MiRNAs, small, non-coding RNAs contribute to the fine tuning of signaling pathways and reciprocal regulation between GCs and miRNAs has been suggested. Our aim was to investigate the expressional change and potential function of GC mediated miRNAs. The miRNA expression profile was measured in three models: human adrenocortical adenoma vs. normal tissue, steroid-producing H295R cells and in hormonally inactive HeLa cells before and after dexamethasone treatment. The gene expression profile in 82 control and 57 GC-affected samples was evaluated in GC producing and six different GC target tissue types. Tissue-specific target prediction (TSTP) was applied to identify the most relevant miRNA−mRNA interactions. Glucocorticoid treatment resulted in cell type-dependent miRNA expression changes. However, 19.5% of the influenced signaling pathways were common in all three experiments, of which the Wnt-signaling pathway seemed to be the most affected. Transcriptome data and TSTP showed similar results, as the Wnt pathway was significantly altered in both the GC-producing adrenal gland and all investigated GC target tissue types. In different cell types, different miRNAs led to the regulation of similar pathways. Wnt signaling may be one of the most important signaling pathways affected by hypercortisolism. It is, at least in part, regulated by miRNAs that mediate the glucocorticoid effect. Our findings on GC producing and GC target tissues suggest that the alteration of Wnt signaling (together with other pathways) may be responsible for the leading symptoms observed in Cushing’s syndrome. |
| first_indexed | 2024-03-10T06:00:53Z |
| format | Article |
| id | doaj.art-99318f6957b949ba87b9f77b5488d4a6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:00:53Z |
| publishDate | 2021-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-99318f6957b949ba87b9f77b5488d4a62023-11-22T20:57:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211177810.3390/ijms222111778Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAsHenriett Butz0Katalin Mészáros1István Likó2Attila Patocs3Hereditary Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, H-1089 Budapest, HungaryHereditary Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, H-1089 Budapest, HungaryHereditary Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, H-1089 Budapest, HungaryHereditary Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, H-1089 Budapest, HungaryGlucocorticoids (GCs) are pleiotropic hormones which regulate innumerable physiological processes. Their comprehensive effects are due to the diversity of signaling mechanism networks. MiRNAs, small, non-coding RNAs contribute to the fine tuning of signaling pathways and reciprocal regulation between GCs and miRNAs has been suggested. Our aim was to investigate the expressional change and potential function of GC mediated miRNAs. The miRNA expression profile was measured in three models: human adrenocortical adenoma vs. normal tissue, steroid-producing H295R cells and in hormonally inactive HeLa cells before and after dexamethasone treatment. The gene expression profile in 82 control and 57 GC-affected samples was evaluated in GC producing and six different GC target tissue types. Tissue-specific target prediction (TSTP) was applied to identify the most relevant miRNA−mRNA interactions. Glucocorticoid treatment resulted in cell type-dependent miRNA expression changes. However, 19.5% of the influenced signaling pathways were common in all three experiments, of which the Wnt-signaling pathway seemed to be the most affected. Transcriptome data and TSTP showed similar results, as the Wnt pathway was significantly altered in both the GC-producing adrenal gland and all investigated GC target tissue types. In different cell types, different miRNAs led to the regulation of similar pathways. Wnt signaling may be one of the most important signaling pathways affected by hypercortisolism. It is, at least in part, regulated by miRNAs that mediate the glucocorticoid effect. Our findings on GC producing and GC target tissues suggest that the alteration of Wnt signaling (together with other pathways) may be responsible for the leading symptoms observed in Cushing’s syndrome.https://www.mdpi.com/1422-0067/22/21/11778miRNAWnt signalingCushingadrenalhypercortisolism |
| spellingShingle | Henriett Butz Katalin Mészáros István Likó Attila Patocs Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAs International Journal of Molecular Sciences miRNA Wnt signaling Cushing adrenal hypercortisolism |
| title | Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAs |
| title_full | Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAs |
| title_fullStr | Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAs |
| title_full_unstemmed | Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAs |
| title_short | Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAs |
| title_sort | wnt signaling regulated by glucocorticoid induced mirnas |
| topic | miRNA Wnt signaling Cushing adrenal hypercortisolism |
| url | https://www.mdpi.com/1422-0067/22/21/11778 |
| work_keys_str_mv | AT henriettbutz wntsignalingregulatedbyglucocorticoidinducedmirnas AT katalinmeszaros wntsignalingregulatedbyglucocorticoidinducedmirnas AT istvanliko wntsignalingregulatedbyglucocorticoidinducedmirnas AT attilapatocs wntsignalingregulatedbyglucocorticoidinducedmirnas |