{"id":2700,"date":"2021-08-10T12:11:22","date_gmt":"2021-08-10T10:11:22","guid":{"rendered":"http:\/\/www.isidorolab.com\/public\/?p=2700"},"modified":"2021-09-05T12:13:46","modified_gmt":"2021-09-05T10:13:46","slug":"identification-of-gna12-driven-gene-signatures-and-key-signaling-networks-in-ovarian-cancer","status":"publish","type":"post","link":"https:\/\/www.isidorolab.com\/public\/index.php\/2021\/08\/10\/identification-of-gna12-driven-gene-signatures-and-key-signaling-networks-in-ovarian-cancer\/","title":{"rendered":"Identification of GNA12-driven gene signatures and key signaling networks in ovarian cancer"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"2700\" class=\"elementor elementor-2700\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-6ad2b8a8 elementor-section-stretched elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"6ad2b8a8\" data-element_type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-72b31b68\" data-id=\"72b31b68\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-626d1583 elementor-widget elementor-widget-text-editor\" data-id=\"626d1583\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Ha+JH&amp;cauthor_id=34429759\">Ji-Hee Ha<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Jayaraman+M&amp;cauthor_id=34429759\">Muralidharan Jayaraman<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Yan+M&amp;cauthor_id=34429759\">Mingda Yan<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Dhanasekaran+P&amp;cauthor_id=34429759\">Padmaja Dhanasekaran<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Isidoro+C&amp;cauthor_id=34429759\">Ciro Isidoro<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-3\"> 3 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Song+YS&amp;cauthor_id=34429759\">Yong-Sang Song<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-4\"> 4 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Dhanasekaran+DN&amp;cauthor_id=34429759\">Danny N Dhanasekaran<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34429759\/#affiliation-2\"> 2<\/a><\/sup><\/p>\n<p>\u00a0<\/p>\n\n<h3 class=\"wp-block-heading\">Affiliations<\/h3>\n\n<p><sup>1<\/sup> Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA.<\/p>\n<p><sup>2<\/sup> Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA.<\/p>\n<p><sup>3<\/sup> Laboratory of Molecular Pathology and NanoBioImaging, Department of Health Sciences, University of Eastern Piedmont, I-17-28100 Novara, Italy.<\/p>\n<p><sup>4<\/sup> Department of Obstetrics and Gynecology, Cancer Research Institute, College of Medicine, Seoul National University, Seoul 151-921, Republic of Korea.<\/p>\n<p>\u00a0<\/p>\n\n<p>PMID: <strong>34429759<\/strong><\/p>\n<p>PMCID: <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/pmc8371953\/\" target=\"_blank\" rel=\"noreferrer noopener\">PMC8371953<\/a><\/p>\n<p>DOI: <a href=\"https:\/\/doi.org\/10.3892\/ol.2021.12980\" target=\"_blank\" rel=\"noreferrer noopener\">10.3892\/ol.2021.12980<\/a><\/p>\n\n<p>\u00a0<\/p>\n<p>Oncol Lett. 2021 Oct;22(4):719. doi: 10.3892\/ol.2021.12980. Epub 2021 Aug 10.<\/p>\n<p>\u00a0<\/p>\n<hr \/>\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n<p>With the focus on defining the oncogenic network stimulated by lysophosphatidic acid (LPA) in ovarian cancer, the present study sought to interrogate the oncotranscriptome regulated by the LPA-mediated signaling pathway. LPA, LPA-receptor (LPAR) and LPAR-activated G protein 12 \u03b1-subunit, encoded by G protein subunit \u03b1 12 (<em>GNA12<\/em>), all serve an important role in ovarian cancer progression. While the general signaling mechanism regulated by LPA\/LPAR\/<em>GNA12<\/em> has previously been characterized, the global transcriptomic network regulated by <em>GNA12<\/em> in ovarian cancer pathophysiology remains largely unknown. To define the LPA\/LPAR\/<em>GNA12<\/em>-orchestrated oncogenic networks in ovarian cancer, transcriptomic and bioinformatical analyses were conducted using SKOV3 cells, in which the expression of <em>GNA12<\/em> was silenced. Array analysis was performed in Agilent SurePrint G3 Human Comparative Genomic Hybridization 8\u00d760 microarray platform. The array results were validated using Kuramochi cells. Gene and functional enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery, Search Tool for Retrieval of Interacting Genes and Cytoscape algorithms. The results indicated a paradigm in which <em>GNA12<\/em> drove ovarian cancer progression by upregulating a pro-tumorigenic network with <em>AKT1, VEGFA, TGFB1, BCL2L1, STAT3<\/em>, insulin-like growth factor 1 and growth hormone releasing hormone as critical hub and\/or bottleneck nodes. Moreover, <em>GNA12<\/em> downregulated a growth-suppressive network involving proteasome 20S subunit (PSM) \u03b26, <em>PSM<\/em> \u03b16, <em>PSM<\/em> ATPase 5, ubiquitin conjugating enzyme E2 E1, <em>PSM<\/em> non-ATPase 10, NDUFA4 mitochondrial complex-associated, NADH:ubiquinone oxidoreductase subunit B8 and anaphase promoting complex subunit 1 as hub or bottleneck nodes. In addition to providing novel insights into the LPA\/LPAR\/<em>GNA12<\/em>-regulated oncogenic networks in ovarian cancer, the present study identified several potential nodes in this network that could be assessed for targeted therapy.<\/p>\n<p>\u00a0<\/p>\n<p>\u00a0<\/p>\n\n<p><strong>Keywords:<\/strong> G protein subunit \u03b1 12; gene expression; genomics; lysophosphatidic acid; ovarian cancer; signaling-network.<\/p>\n\n<p>\u00a0<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t<div style='text-align:center' class='yasr-auto-insert-visitor'><!--Yasr Visitor Votes Shortcode--><div id='yasr_visitor_votes_15d96729161f7' class='yasr-visitor-votes'><div class=\"yasr-custom-text-vv-before yasr-custom-text-vv-before-2700\">Clicca per votare questo articolo!<\/div><div id='yasr-vv-second-row-container-15d96729161f7'\r\n                                        class='yasr-vv-second-row-container'><div id='yasr-visitor-votes-rater-15d96729161f7'\r\n                                      class='yasr-rater-stars-vv'\r\n                                      data-rater-postid='2700'\r\n                                      data-rating='0'\r\n                                      data-rater-starsize='32'\r\n                                      data-rater-readonly='false'\r\n                                      data-rater-nonce='9e55f43059'\r\n                                      data-issingular='false'\r\n                                    ><\/div><div class=\"yasr-vv-stats-text-container\" id=\"yasr-vv-stats-text-container-15d96729161f7\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" width=\"20\" height=\"20\"\r\n                                   class=\"yasr-dashicons-visitor-stats\"\r\n                                   data-postid=\"2700\"\r\n                                   id=\"yasr-stats-dashicon-15d96729161f7\">\r\n                                   <path d=\"M18 18v-16h-4v16h4zM12 18v-11h-4v11h4zM6 18v-8h-4v8h4z\"><\/path>\r\n                               <\/svg><span id=\"yasr-vv-text-container-15d96729161f7\" class=\"yasr-vv-text-container\">[Total: <span id=\"yasr-vv-votes-number-container-15d96729161f7\">0<\/span>  Average: <span id=\"yasr-vv-average-container-15d96729161f7\">0<\/span>]<\/span><\/div><div id='yasr-vv-loader-15d96729161f7' class='yasr-vv-container-loader'><\/div><\/div><div id='yasr-vv-bottom-container-15d96729161f7' class='yasr-vv-bottom-container'><\/div><\/div><!--End Yasr Visitor Votes Shortcode--><\/div>","protected":false},"excerpt":{"rendered":"<p>Ji-Hee Ha\u00a0 1 \u00a0 2 ,\u00a0Muralidharan Jayaraman\u00a0 1 \u00a0 2 ,\u00a0Mingda Yan\u00a0 1 ,\u00a0Padmaja Dhanasekaran\u00a0 1 ,\u00a0Ciro Isidoro\u00a0 3 ,\u00a0Yong-Sang Song\u00a0 4 ,\u00a0Danny N Dhanasekaran\u00a0 1 \u00a0 2 \u00a0 Affiliations 1 Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA. 2 Department of Cell Biology, The University of Oklahoma Health&hellip;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"yasr_overall_rating":0,"yasr_post_is_review":"","yasr_auto_insert_disabled":"","yasr_review_type":"","footnotes":""},"categories":[136],"tags":[62],"class_list":["post-2700","post","type-post","status-publish","format-standard","hentry","category-paper","tag-ovarian-cancer"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - 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