{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:01:36Z","timestamp":1775800896483,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T00:00:00Z","timestamp":1619913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T00:00:00Z","timestamp":1619913600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>\n                    Pregnancy\u2010associated plasma protein A (PAPP\u2010A) is a proteolytic enzyme produced by the placenta. The expression and role of PAPP\u2010A in renal cell carcinoma (RCC) remain elusive. The aim of this study was to investigate the role and the molecular mechanisms of PAPP\u2010A in RCC. Initially, we evaluated the expression of PAPP\u2010A in samples from patients with RCC and cell lines by quantitative PCR, western blot and immunohistochemical staining, and examined the role of PAPP\u2010A in RCC cells by cell viability, colony formation and Transwell assays. Next, we investigated the molecular mechanisms regulating the tumor suppressor function of PAPP\u2010A. Our results demonstrated that PAPP\u2010A is expressed at low levels in RCC tissues and cells. Clinical data analysis revealed a significant correlation between PAPP\u2010A expression and RCC\u2010related death (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.0115). Overexpression of PAPP\u2010A inhibited viability, proliferation, migration and invasion of RCC cells. Furthermore, PAPP\u2010A overexpression significantly increased phosphorylation of c\u2010Jun N\u2010terminal kinase and decreased the expression of cyclin D1, phosphorylated glycogen synthase kinase\u20103\u03b2 and \u03b2\u2010catenin. This study is the first to report that downregulation of PAPP\u2010A is associated with poor prognosis in patients with RCC. In conclusion, PAPP\u2010A may serve as a novel prognostic marker and potentially as a therapeutic target in patients with RCC.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.13156","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T11:01:16Z","timestamp":1617188476000},"page":"1593-1606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PAPP\u2010A functions as a tumor suppressor and is downregulated in renal cell carcinoma"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4598-3015","authenticated-orcid":false,"given":"Yanxin","family":"Lu","sequence":"first","affiliation":[{"name":"Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University China"},{"name":"Zhuhai Campus of Zunyi Medical University China"},{"name":"Shenzhen Institute of Advanced Technology Chinese Academy of Science Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University China"},{"name":"Shenzhen Key Laboratory of Genitourinary Tumor Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University China"},{"name":"Shenzhen Key Laboratory of Genitourinary Tumor Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University 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