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      PLAU Promotes Cell Proliferation and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma

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          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.

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          Most cited references41

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          Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

          The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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            GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

            Abstract Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.
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              TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

              Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. Cancer Res; 77(21); e108-10. ©2017 AACR.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                20 May 2021
                2021
                : 12
                : 651882
                Affiliations
                [1] 1Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [2] 2School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [3] 3Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration , Wuhan, China
                Author notes

                Edited by: Manoj Kumar Kashyap, Amity University Gurgaon, India

                Reviewed by: Yashwanth Subbannayya, Norwegian University of Science and Technology, Norway; Harrys Kishore Charles Jacob, University of Miami Health System, United States

                *Correspondence: Qingming Tang, hust_tang@ 123456hust.edu.cn

                These authors have contributed equally to this work

                This article was submitted to Cancer Genetics, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2021.651882
                8173099
                34093649
                eeadc2ad-857c-40d5-babd-905fcf2f374e
                Copyright © 2021 Chen, Sun, Xie, Yu, Tang and Chen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 January 2021
                : 23 April 2021
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 41, Pages: 14, Words: 0
                Categories
                Genetics
                Original Research

                Genetics
                prognostic biomarker,emt,plau,tnfrsf12a,head and neck squamous cell carcinoma
                Genetics
                prognostic biomarker, emt, plau, tnfrsf12a, head and neck squamous cell carcinoma

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