{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:47:01Z","timestamp":1788878821184,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T00:00:00Z","timestamp":1646438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2021\/05\/X\/NZ5\/01874"],"award-info":[{"award-number":["2021\/05\/X\/NZ5\/01874"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Corticotroph pituitary adenomas commonly cause Cushing\u2019s disease (CD), but some of them are clinically silent. The reason why they do not cause endocrinological symptoms remains unclear. We used data from small RNA sequencing in adenomas causing CD (n = 28) and silent ones (n = 20) to explore the role of miRNA in hormone secretion and clinical status of the tumors. By comparing miRNA profiles, we identified 19 miRNAs differentially expressed in clinically functioning and silent corticotroph adenomas. The analysis of their putative target genes indicates a role of miRNAs in regulation of the corticosteroid receptors expression. Adenomas causing CD have higher expression of hsa-miR-124-3p and hsa-miR-135-5p and lower expression of their target genes NR3C1 and NR3C2. The role of hsa-miR-124-3p in the regulation of NR3C1 was further validated in vitro using AtT-20\/D16v-F2 cells. The cells transfected with miR-124-3p mimics showed lower levels of glucocorticoid receptor expression than control cells while the interaction between miR-124-3p and NR3C1 3\u2032 UTR was confirmed using luciferase reporter assay. The results indicate a relatively small difference in miRNA expression between clinically functioning and silent corticotroph pituitary adenomas. High expression of hsa-miR-124-3p in adenomas causing CD plays a role in the regulation of glucocorticoid receptor level and probably in reducing the effect of negative feedback mediated by corticosteroids.<\/jats:p>","DOI":"10.3390\/ijms23052867","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:38:16Z","timestamp":1646599096000},"page":"2867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Difference in miRNA Expression in Functioning and Silent Corticotroph Pituitary Adenomas Indicates the Role of miRNA in the Regulation of Corticosteroid Receptors"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0948-1763","authenticated-orcid":false,"given":"Beata J.","family":"Mossakowska","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Kober","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Rusetska","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Boresowicz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Maksymowicz","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"P\u0119kul","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Zieli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Military Institute of Medicine, 04-141 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Styk","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Military Institute of Medicine, 04-141 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Kunicki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Mandat","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Bujko","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s11102-018-0864-8","article-title":"Silent Corticotroph Adenomas","volume":"21","author":"Cooper","year":"2018","journal-title":"Pituitary"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s12020-016-1038-y","article-title":"Pituitary Magnetic Resonance Imaging in Cushing\u2019s Disease","volume":"55","author":"Vitale","year":"2017","journal-title":"Endocrine"},{"key":"ref_3","first-page":"3","article-title":"High-Risk Pituitary Adenomas and Strategies for Predicting Response to Treatment","volume":"1","author":"Kontogeorgos","year":"2022","journal-title":"Hormones"},{"key":"ref_4","unstructured":"Lloyd, R.V., Osamura, R.Y., and Rosari, J. 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