{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T05:06:30Z","timestamp":1755839190766,"version":"3.41.0"},"reference-count":46,"publisher":"Canadian Science Publishing","issue":"5","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Biochem. Cell Biol."],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p> Tuberous sclerosis complex (TSC), an inherited neurocutaneous disease, is caused by mutations in either the TSC1 or TSC2 gene. This genetic disorder is characterized by the growth of benign tumors in the brain, kidneys, and other organs. As a member of the orphan nuclear receptor family, nuclear receptor related 1 (Nurr1) plays a vital role in some neuropathological diseases and several types of benign or malignant tumors. Here, we explored the potential regulatory role of TSC1\/2 signaling in Nurr1 and the effect of Nurr1 in TSC-related tumors. We found that Nurr1 expression was drastically decreased by the disruption of the TSC1\/2 complex in Tsc2-null cells, genetically modified mouse models of TSC, cortical tubers of TSC patients, and kidney tumor tissue obtained from a TSC patient. Deficient TSC1\/2 complex downregulated Nurr1 expression in an mTOR-dependent manner. Moreover, hyperactivation of mTOR reduced Nurr1 expression via suppression of autophagy. In addition, Nurr1 overexpression inhibited cell proliferation and suppressed cell cycle progression. Therefore, TSC\/mTOR\/autophagy\/Nurr1 signaling is partially responsible for the tumorigenesis of TSC. Taken together, Nurr1 may be a novel therapeutic target for TSC-associated tumors, and Nurr1 agonists or reagents that induce Nurr1 expression may be used for the treatment of TSC. <\/jats:p>","DOI":"10.1139\/bcb-2021-0017","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T16:35:22Z","timestamp":1630427722000},"page":"570-577","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Aberrant mTOR\/autophagy\/Nurr1 signaling is critical for TSC-associated tumor development"],"prefix":"10.1139","volume":"99","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Molecular Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunjia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanzhuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongdong","family":"Hu","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengai","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr393"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.04.004"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15868"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2009.00341.x"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.885673"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500451200"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00069-1"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.209"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3609"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.05.008"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i47.6865"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28228"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.06.001"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00052-1"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-0923-1"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0730"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24737"},{"key":"refg18\/ref18","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2019.0718"},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw397"},{"issue":"1","key":"refg20\/ref20","first-page":"26","volume":"42","author":"Lagos J.C.","year":"1967","journal-title":"Mayo Clin. 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