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Transcriptional and epigenetic regulation of\n                    <jats:italic>SSTR5<\/jats:italic>\n                    gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript,\n                    <jats:italic>SSTR5\u2010AS1<\/jats:italic>\n                    , potentially regulating\n                    <jats:italic>SSTR5<\/jats:italic>\n                    expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of\n                    <jats:italic>SSTR5<\/jats:italic>\n                    expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the\n                    <jats:italic>SSTR5<\/jats:italic>\n                    \/\n                    <jats:italic>SSTR5\u2010AS1<\/jats:italic>\n                    human locus\n                    <jats:italic>in\u2009silico<\/jats:italic>\n                    to identify CpG islands.\n                    <jats:italic>SSTR5<\/jats:italic>\n                    and\n                    <jats:italic>SSTR5\u2010AS1<\/jats:italic>\n                    expression was assessed by quantitative real\u2010time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs\/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the\n                    <jats:italic>SSTR5<\/jats:italic>\n                    \/\n                    <jats:italic>SSTR5\u2010AS1<\/jats:italic>\n                    genes. Results revealed that\n                    <jats:italic>SSTR5<\/jats:italic>\n                    and\n                    <jats:italic>SSTR5\u2010AS1<\/jats:italic>\n                    were directly correlated in NP, somatotropinoma, and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines,\n                    <jats:italic>SSTR5\u2010AS1<\/jats:italic>\n                    silencing downregulated\n                    <jats:italic>SSTR5<\/jats:italic>\n                    expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that\n                    <jats:italic>SSTR5<\/jats:italic>\n                    expression in PitNETs and PanNETs can be epigenetically regulated by the\n                    <jats:italic>SSTR5\u2010AS1<\/jats:italic>\n                    antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13107","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T13:18:58Z","timestamp":1633353538000},"page":"764-779","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Epigenetic and post\u2010transcriptional regulation of somatostatin receptor subtype 5 (SST\n                    <sub>5<\/sub>\n                    ) in pituitary and pancreatic neuroendocrine tumors"],"prefix":"10.1002","volume":"16","author":[{"given":"Sergio","family":"Pedraza\u2010Arevalo","sequence":"first","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Department of Cell Biology, Physiology, and Immunology University of C\u00f3rdoba C\u00f3rdoba Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn) C\u00f3rdoba Spain"},{"name":"Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4649-0095","authenticated-orcid":false,"given":"Alejandro","family":"Ib\u00e1\u00f1ez\u2010Costa","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Department of Cell Biology, Physiology, and Immunology University of C\u00f3rdoba C\u00f3rdoba Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn) C\u00f3rdoba Spain"},{"name":"Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Bl\u00e1zquez\u2010Encinas","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Department of Cell Biology, Physiology, and Immunology University of C\u00f3rdoba C\u00f3rdoba Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn) C\u00f3rdoba Spain"},{"name":"Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel R.","family":"Branco","sequence":"additional","affiliation":[{"name":"Blizard Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari C.","family":"V\u00e1zquez\u2010Borrego","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Department of Cell Biology, Physiology, and Immunology University of C\u00f3rdoba C\u00f3rdoba Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn) C\u00f3rdoba Spain"},{"name":"Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aura D.","family":"Herrera\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Endocrinology and Nutrition Service Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Venegas\u2010Moreno","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Unit Hospital Universitario Virgen del Roc\u00edo Instituto de Biomedicina de Sevilla (IBIS) Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Serrano\u2010Blanch","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Medical Oncology Service Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Arjona\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Surgery Service Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda A.","family":"G\u00e1lvez\u2010Moreno","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Endocrinology and Nutrition Service Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Korbonits","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Soto\u2010Moreno","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Unit Hospital Universitario Virgen del Roc\u00edo Instituto de Biomedicina de Sevilla (IBIS) Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-2179","authenticated-orcid":false,"given":"Manuel D.","family":"Gahete","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Department of Cell Biology, Physiology, and Immunology University of C\u00f3rdoba C\u00f3rdoba Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn) C\u00f3rdoba Spain"},{"name":"Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Charalambous","sequence":"additional","affiliation":[{"name":"Developmental Epigenetics group Department of Medical and Molecular Genetics King\u2019s College of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal M.","family":"Luque","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Department of Cell Biology, Physiology, and Immunology University of C\u00f3rdoba C\u00f3rdoba Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn) C\u00f3rdoba Spain"},{"name":"Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3145-7287","authenticated-orcid":false,"given":"Justo P.","family":"Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC) C\u00f3rdoba Spain"},{"name":"Department of Cell Biology, Physiology, and Immunology University of C\u00f3rdoba C\u00f3rdoba Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn) C\u00f3rdoba Spain"},{"name":"Reina Sofia University Hospital C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-018-9465-0"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-1033-0"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-18-0354"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0589"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/21548331.2016.1210474"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01479-y"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0560"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.19699"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-17-0004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-019-00988-2"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-019-01027-w"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-010-0253-4"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0391-1977.19.02970-5"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0071-6"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566524011313040008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.015388"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-16-0151"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.12.003"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05511.x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002590100541"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.01.037"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-017-1482-3"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00445.2012"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.10.001"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6565"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(84)90706-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-015-0677-y"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316158"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0002"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2013.07.005"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1460707"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2013.49.2.1915142"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.11.007"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-021-00514-0"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2017.04.004"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112009"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11091302"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-019-0283-8"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030691"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-14-0304"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(91)90004-5"},{"key":"e_1_2_11_43_1","first-page":"596","article-title":"Establishment 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