{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:54:28Z","timestamp":1753883668508,"version":"3.41.2"},"reference-count":34,"publisher":"The Endocrine Society","issue":"11","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["1ZIADK075035"],"award-info":[{"award-number":["1ZIADK075035"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Maternally expressed gene 3 (MEG3) is a long noncoding RNA (lncRNA) that has been implicated as a tumor suppressor.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The expression of MEG3 RNA is downregulated in various human tumors, including pituitary adenoma and pancreatic islet tumors due to MEG3 gene deletion or DNA hypermethylation. Mouse models with conventional germline deletion of Meg3 have shown that Meg3 is essential for perinatal or postnatal development and survival. However, a direct role of Meg3 loss in tumorigenesis has not been shown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To observe a causal relationship between Meg3 loss and tumorigenesis, we have generated a mouse model with conditional deletion of Meg3 mediated by the RIP-Cre transgene that initiated Meg3 deletion in pancreatic islet \u03b2 cells and anterior pituitary.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Meg3 loss did not lead to the development of islet tumors. Interestingly, RIP-Cre\u2013mediated Meg3 loss led to the development of an enlarged pituitary. The genes in the Meg3 region are transcribed together as a 210\u2005kb RNA that is processed into Meg3 and other transcripts. Whether these tandem transcripts play a functional role in the growth of pancreatic endocrine cells and pituitary cells remains to be determined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our mouse model shows that Meg3 loss leads to hyperplasia in the pituitary and not in pancreatic islets, thus serving as a valuable model to study pathways associated with pituitary cell proliferation and function. Future mouse models with specific inactivation of Meg3 alone or other transcripts in the Meg3 polycistron are warranted to study tissue-specific effects on initiating neoplasia and tumor development.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvac141","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T19:14:26Z","timestamp":1663096466000},"source":"Crossref","is-referenced-by-count":0,"title":["Mice With RIP-Cre\u2013mediated Deletion of the Long Noncoding RNA <i>Meg3<\/i> Show Normal Pancreatic Islets and Enlarged Pituitary"],"prefix":"10.1210","volume":"6","author":[{"given":"Vaishali I","family":"Parekh","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892-1802 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892-1802 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892-1802 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee S","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892-1802 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7557-3191","authenticated-orcid":false,"given":"Sunita K","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892-1802 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"issue":"3","key":"2023061204353802800_bvac141-B1","doi-asserted-by":"crossref","first-page":"R45","DOI":"10.1530\/JME-12-0008","article-title":"MEG3 noncoding RNA: a tumor suppressor","volume":"48","author":"Zhou","year":"2012","journal-title":"J Mol Endocrinol"},{"issue":"18","key":"2023061204353802800_bvac141-B2","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/S0960-9822(00)00704-1","article-title":"Delta-like and gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12","volume":"10","author":"Takada","year":"2000","journal-title":"Curr Biol"},{"issue":"6","key":"2023061204353802800_bvac141-B3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000992","article-title":"The IG-DMR and the MEG3-DMR at human chromosome 14q32.2: hierarchical interaction and distinct functional properties as imprinting control centers","volume":"6","author":"Kagami","year":"2010","journal-title":"PLoS Genet"},{"issue":"12","key":"2023061204353802800_bvac141-B4","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1101\/gr.206901","article-title":"Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region","volume":"11","author":"Paulsen","year":"2001","journal-title":"Genome 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