{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:38:02Z","timestamp":1789097882265,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T00:00:00Z","timestamp":1658534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004773","name":"Henan University","doi-asserted-by":"publisher","award":["20IRTSTHN026"],"award-info":[{"award-number":["20IRTSTHN026"]}],"id":[{"id":"10.13039\/501100004773","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ19H160005"],"award-info":[{"award-number":["LQ19H160005"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ18H160002"],"award-info":[{"award-number":["LZ18H160002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972908"],"award-info":[{"award-number":["81972908"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the function of PAQR3 in gastric cardia adenocarcinoma (GCA) and understand the possible mechanism of PAQR3 in regulating epithelial\u2013mesenchymal transition (EMT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We detected PAQR3 protein in 146 GCA tissues and paired normal adjacent tissues (PNTs) specimens using immunohistochemical analysis, and explored its clinical significance. The expression levels of PAQR3 protein in 20 GCA tissues, their paired PNTs, HGC27, SGC7901, and GES\u20101 cells were analyzed by Western blot. Wild\u2010type PAQR3 was overexpressed in HGC27 cells. The effects of PAQR3 overexpression on the function of HGC27 cells and its underlying mechanisms were then analyzed through a series of cell and molecular biology experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PAQR3 was significantly down\u2010regulated in GCA tissues when compared with paired PNTs (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). The expression level of PAQR3 in GCA tissues was significantly negatively correlated with <jats:italic>Helicobacter pylori<\/jats:italic> infection (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.000), venous invasion (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.000), invasion depth (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.000), lymph node metastasis (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.022), tumor stage (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.000), and patient survival (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.009). Downregulation of PAQR3 was highly correlated with increased EMT signature and activated TGF\u2010\u03b2\/Smad pathway in GCA tissues. Overexpression of PAQR3 in HGC27 cells negatively regulates its cellular functions, such as cell proliferation and migration, and suppresses EMT. Mechanistically, overexpression of PAQR3 significantly down\u2010regulates the protein expression levels of TGF\u20101, p\u2010Smad2, and p\u2010Smad3 in HGC27 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PAQR3 was significantly down\u2010regulated in GCA tissues, HGC27, and SGC7901 cells. PAQR3 significantly inhibits the proliferation, migration, and invasion of HGC27 cells. Mechanistically, PAQR3 can inhibit the EMT process in HGC27 cells by regulating TGF\u2010\u03b2\/Smad signaling pathway.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24617","type":"journal-article","created":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T19:04:42Z","timestamp":1658603082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Golgi scaffold protein <scp>PAQR3<\/scp> as a candidate suppressor of gastric cardia adenocarcinoma via regulating <scp>TGF<\/scp>\u2010\u03b2\/Smad pathway"],"prefix":"10.1002","volume":"36","author":[{"given":"Ying\u2010Li","family":"Wu","sequence":"first","affiliation":[{"name":"Zhejiang Cancer Institute Cancer Hospital of the University of Chinese Academy of Sciences; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences  Hangzhou China"},{"name":"Department of anaesthesiology Cancer Hospital of the University of Chinese Academy of Sciences; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian\u2010Lian","family":"Hong","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Institute Cancer Hospital of the University of Chinese Academy of Sciences; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe\u2010Nan","family":"Ling","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan\u2010Yu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Institute Cancer Hospital of the University of Chinese Academy of Sciences; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medical Sciences  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2155-1111","authenticated-orcid":false,"given":"Zhi\u2010Qiang","family":"Ling","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Institute Cancer Hospital of the University of Chinese Academy of Sciences; 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