{"id":2709,"date":"2021-08-14T12:17:57","date_gmt":"2021-08-14T10:17:57","guid":{"rendered":"http:\/\/www.isidorolab.com\/public\/?p=2709"},"modified":"2021-09-05T12:19:43","modified_gmt":"2021-09-05T10:19:43","slug":"gnai2-gip2-regulated-transcriptome-and-its-therapeutic-significance-in-ovarian-cancer","status":"publish","type":"post","link":"http:\/\/www.isidorolab.com\/public\/index.php\/2021\/08\/14\/gnai2-gip2-regulated-transcriptome-and-its-therapeutic-significance-in-ovarian-cancer\/","title":{"rendered":"GNAi2\/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"2709\" class=\"elementor elementor-2709\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-4772f4bd elementor-section-stretched elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"4772f4bd\" 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-265be11b\" data-id=\"265be11b\" 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-52dae506 elementor-widget elementor-widget-text-editor\" data-id=\"52dae506\" 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=34439877\">Ji Hee Ha<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Jayaraman+M&amp;cauthor_id=34439877\">Muralidharan Jayaraman<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Yan+M&amp;cauthor_id=34439877\">Mingda Yan<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Dhanasekaran+P&amp;cauthor_id=34439877\">Padmaja Dhanasekaran<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Isidoro+C&amp;cauthor_id=34439877\">Ciro Isidoro<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-3\"> 3 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Song+YS&amp;cauthor_id=34439877\">Yong Sang Song<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-4\"> 4 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Dhanasekaran+DN&amp;cauthor_id=34439877\">Danny N Dhanasekaran<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34439877\/#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 City, OK 73104, USA.<\/p>\n<p><sup>2<\/sup> Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.<\/p>\n<p><sup>3<\/sup> Laboratory of Molecular Pathology and NanoBioImaging, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale, 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, Korea.<\/p>\n<p>\u00a0<\/p>\n\n<p>PMID: <strong>34439877<\/strong><\/p>\n<p>PMCID: <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/pmc8393559\/\" target=\"_blank\" rel=\"noreferrer noopener\">PMC8393559<\/a><\/p>\n<p>DOI: <a href=\"https:\/\/doi.org\/10.3390\/biom11081211\" target=\"_blank\" rel=\"noreferrer noopener\">10.3390\/biom11081211<\/a><\/p>\n\n<p>Biomolecules. 2021 Aug 14;11(8):1211. doi: 10.3390\/biom11081211.<\/p>\n<p>\u00a0<\/p>\n<hr \/>\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n<p>Increased expression of <em>GNAi2<\/em>, which encodes the \u03b1-subunit of G-protein i2, has been correlated with the late-stage progression of ovarian cancer. <em>GNAi2<\/em>, also referred to as the proto-oncogene <em>gip2<\/em>, transduces signals from lysophosphatidic acid (LPA)-activated LPA-receptors to oncogenic cellular responses in ovarian cancer cells. To identify the oncogenic program activated by <em>gip2<\/em>, we carried out micro-array-based transcriptomic and bioinformatic analyses using the ovarian cancer cell-line SKOV3, in which the expression of <em>GNAi2<\/em>\/<em>gip2<\/em> was silenced by specific shRNA. A cut-off value of 5-fold change in gene expression (<em>p<\/em> &lt; 0.05) indicated that a total of 264 genes were dependent upon <em>gip2<\/em>-expression with 136 genes coding for functional proteins. Functional annotation of the transcriptome indicated the hitherto unknown role of <em>gip2<\/em> in stimulating the expression of oncogenic\/growth-promoting genes such as KDR\/VEGFR2, CCL20, and VIP. The array results were further validated in a panel of High-Grade Serous Ovarian Carcinoma (HGSOC) cell lines that included Kuramochi, OVCAR3, and OVCAR8 cells. Gene set enrichment analyses using DAVID, STRING, and Cytoscape applications indicated the potential role of the <em>gip2<\/em>-stimulated transcriptomic network involved in the upregulation of cell proliferation, adhesion, migration, cellular metabolism, and therapy resistance. The results unravel a multi-modular network in which the hub and bottleneck nodes are defined by ACKR3\/CXCR7, IL6, VEGFA, CYCS, COX5B, UQCRC1, UQCRFS1, and FYN. The identification of these genes as the critical nodes in <em>GNAi2\/gip2<\/em> orchestrated onco-transcriptome establishes their role in ovarian cancer pathophysiology. In addition, these results also point to these nodes as potential targets for novel therapeutic strategies.<\/p>\n<p>\u00a0<\/p>\n<p>\u00a0<\/p>\n\n<p><strong>Keywords:<\/strong> GNAi2; bio-informatics; gene expression; gip2; ovarian cancer; transcriptome.<\/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_770162916eae5' class='yasr-visitor-votes'><div class=\"yasr-custom-text-vv-before yasr-custom-text-vv-before-2709\">Clicca per votare questo articolo!<\/div><div id='yasr-vv-second-row-container-770162916eae5'\r\n                                        class='yasr-vv-second-row-container'><div id='yasr-visitor-votes-rater-770162916eae5'\r\n                                      class='yasr-rater-stars-vv'\r\n                                      data-rater-postid='2709'\r\n                                      data-rating='0'\r\n                                      data-rater-starsize='32'\r\n                                      data-rater-readonly='false'\r\n                                      data-rater-nonce='03bbe589a3'\r\n                                      data-issingular='false'\r\n                                    ><\/div><div class=\"yasr-vv-stats-text-container\" id=\"yasr-vv-stats-text-container-770162916eae5\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" width=\"20\" height=\"20\"\r\n                                   class=\"yasr-dashicons-visitor-stats\"\r\n                                   data-postid=\"2709\"\r\n                                   id=\"yasr-stats-dashicon-770162916eae5\">\r\n                                   <path d=\"M18 18v-16h-4v16h4zM12 18v-11h-4v11h4zM6 18v-8h-4v8h4z\"><\/path>\r\n                               <\/svg><span id=\"yasr-vv-text-container-770162916eae5\" class=\"yasr-vv-text-container\">[Total: <span id=\"yasr-vv-votes-number-container-770162916eae5\">0<\/span>  Average: <span id=\"yasr-vv-average-container-770162916eae5\">0<\/span>]<\/span><\/div><div id='yasr-vv-loader-770162916eae5' class='yasr-vv-container-loader'><\/div><\/div><div id='yasr-vv-bottom-container-770162916eae5' 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 City, OK 73104, USA. 2 Department of Cell Biology, The University&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-2709","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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