{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T13:58:44Z","timestamp":1769263124820,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>MicroRNA\u2010646 (miR\u2010646) has been implicated in several other cancers; however, its functional mechanism in non\u2010small cell lung cancer (NSCLC) remains unclear. In this study, we observed the downregulation of miR\u2010646 expression in NSCLC tissues and cell lines. Low\u2010level expression of miR\u2010646 was associated with metastasis and stage of NSCLCs. Functional assays showed that overexpression of miR\u2010646 could suppress NSCLC cell proliferation, clonogenicity, invasion, and inhibit epithelial\u2010mesenchymal transition (EMT), whereas decreased miR\u2010646 expression showed the opposite effects. Importantly, miR\u2010646 overexpression attenuated in vivo tumor growth and metastasis in nude mice models. Mechanically, miR\u2010646 directly targeted and suppressed fibroblast growth factor 2 (FGF2) and cyclin D2 (CCND2) expression. Reintroduction of FGF2 and CCND2 attenuated miR\u2010646\u2010mediated suppression of proliferation and invasion in NSCLC. Collectively, these results demonstrate that miR\u2010646 acts as a tumor suppressor in NSCLC by targeting FGF2 and CCND2, and may serve as a therapeutic target for patients with NSCLC.<\/jats:p>","DOI":"10.1002\/cam4.3062","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T09:42:14Z","timestamp":1588153334000},"page":"4360-4370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["MiR\u2010646 suppresses proliferation and metastasis of non\u2010small cell lung cancer by repressing FGF2 and CCND2"],"prefix":"10.1002","volume":"9","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Respiratory Disease Jinshan Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huizhen","family":"Shu","sequence":"additional","affiliation":[{"name":"Xuanqiao Community Health Service Center Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0557-8392","authenticated-orcid":false,"given":"Shuigen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease Shanghai Pudong Hospital Fudan University Pudong Medical Center Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25516"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2088"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20107"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.10.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1379"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00428-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.06.006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.19168"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-016-0569-4"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.382"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.181"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00222.2017"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-017-0082-2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.267"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430333"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/01902148.2016.1207726"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60735-0"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6180425"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2014.51"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0882-4"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.3062","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.3062","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.3062","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.3062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T10:46:25Z","timestamp":1692787585000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.3062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,29]]},"references-count":20,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/cam4.3062"],"URL":"https:\/\/doi.org\/10.1002\/cam4.3062","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,29]]},"assertion":[{"value":"2019-07-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}