{"corpus_id":235333055,"paper_sha":"a4e7ce1ff6f724f6084428b8f9ce3356482556b5","doi":"10.3389/fgene.2021.651882","arxiv_id":null,"pmid":34093649,"pmcid":"8173099","mag_id":null,"dblp_id":null,"acl_id":null,"title":"PLAU Promotes Cell Proliferation and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma","year":2021,"publication_date":"2021-05-20","venue":"Frontiers in Genetics","journal":{"name":"Frontiers in Genetics","pages":null,"volume":"12"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":44,"citation_count":55,"influential_citation_count":6,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":null,"chemicals":null,"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.frontiersin.org/articles/10.3389/fgene.2021.651882/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/a4e7ce1ff6f724f6084428b8f9ce3356482556b5","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Plasminogen activator, urokinase (uPA) is a secreted serine protease whose Dysregulation is often accompanied by various cancers. However, the biological functions and potential mechanisms of PLAU in head and neck squamous cell carcinoma (HNSCC) remain undetermined. Here, the expression, prognosis, function, and coexpression genetic networks of PLAU in HNSCC were investigated by a series of public bioinformatics tools. A Higher PLAU level predicted a poorer clinical outcome. Meanwhile, functional network analysis implied that PLAU and associated genes mainly regulated cell-substrate adhesion, tissue migration, and extracellular matrix binding. The top 4 significantly associated genes are C10orf55, ITGA5, SERPINE1, and TNFRSF12A. Pathway enrichment analysis indicated that PLAU might activate the epithelial-to-mesenchymal transition (EMT) process, which could explain the poor prognosis in HNSCC. Besides, genes associated with PLAU were also enriched in EMT pathways. We further validated the bioinformatics analysis results by in vivo and in vitro experiments. Then, we found that much more PLAU was detected in HNSCC tissues, and the silencing of PLAU inhibit the proliferation, migration, and EMT process of CAL27 cell lines. Notably, the downregulation of PLAU decreased the expression of TNFRSF12A. Moreover, knockdown TNFRSF12A also inhibits cell proliferation and migration. In vivo experiment results indicated that PLAU inhibition could suppress tumor growth. Collectively, PLAU is necessary for tumor progression and can be a diagnostic and prognostic biomarker in HNSCC.","claims":[{"public_id":"cl_3f35153f60f4f3c831dee955b4e4e2c1","status":"active","text":"Higher PLAU expression predicts poorer clinical outcome in head and neck squamous cell carcinoma.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_3f35153f60f4f3c831dee955b4e4e2c1"},{"public_id":"cl_700edeebbf8c212655169cb5d476c35a","status":"active","text":"PLAU and its associated genes are mainly linked to cell-substrate adhesion, tissue migration, and extracellular matrix binding.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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(12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_5fdd205f10b4b8bd93f763dc27c6e32a"},{"public_id":"cl_a7932e5a1d533b940673515382c318af","status":"active","text":"Silencing PLAU inhibits proliferation, migration, and epithelial-to-mesenchymal transition in CAL27 cell lines, and PLAU inhibition suppresses tumor growth in vivo.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_a7932e5a1d533b940673515382c318af"},{"public_id":"cl_1a1ffe560836e8e5526299e0a7d34fc6","status":"active","text":"TNFRSF12A downregulation reduces PLAU-associated proliferation and migration, and PLAU knockdown decreases TNFRSF12A expression.","confidence":0.93,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_1a1ffe560836e8e5526299e0a7d34fc6"}],"concepts":[{"public_id":"co_1ab3a2a500266293603c448e2278c3a7","status":"active","name":"head and neck squamous cell carcinoma","description":"A malignant cancer arising from squamous cells in the head and neck region.","types":["cancer"],"aliases":["HNSCC"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_1ab3a2a500266293603c448e2278c3a7"},{"public_id":"co_2e186a7ad0a15faa50d12c5af3e0d4a7","status":"active","name":"tissue migration","description":"The movement of cells or tissues during biological processes such as invasion or metastasis.","types":["biological process"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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(12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_3c77c996a6dfe86a66a2d8e1eff74553"},{"public_id":"co_7e5dcaf4cd6d9bc65ce0baddd13919aa","status":"active","name":"proliferation","description":"Cell division and expansion of cell number measured as a functional outcome.","types":["biological process"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_7e5dcaf4cd6d9bc65ce0baddd13919aa"},{"public_id":"co_8aa593fbfbc0649bda8952b2fa194699","status":"active","name":"PLAU","description":"The gene encoding urokinase plasminogen activator, a secreted serine protease examined for its role in head and neck squamous cell carcinoma.","types":["gene"],"aliases":["uPA","plasminogen activator, urokinase"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_8aa593fbfbc0649bda8952b2fa194699"},{"public_id":"co_8cd90412417a1d7061664a28bc3339e9","status":"active","name":"extracellular matrix binding","description":"Molecular interaction with components of the extracellular matrix.","types":["molecular function"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_8cd90412417a1d7061664a28bc3339e9"},{"public_id":"co_b4a4ed3ed3150fea11b365e4333b0fe4","status":"active","name":"tumor growth","description":"Increase in tumor size or progression measured in vivo.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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