{"id":33410,"date":"2021-12-24T05:49:34","date_gmt":"2021-12-24T05:49:34","guid":{"rendered":"https:\/\/csi.nus.edu.sg\/?p=33410"},"modified":"2022-12-23T02:39:53","modified_gmt":"2022-12-23T02:39:53","slug":"antisense-rnas-influence-promoter-usage-of-their-counterpart-sense-genes-in-cancer-cancer-res-dec-2021","status":"publish","type":"post","link":"https:\/\/csi.nus.edu.sg\/antisense-rnas-influence-promoter-usage-of-their-counterpart-sense-genes-in-cancer-cancer-res-dec-2021\/","title":{"rendered":"Antisense RNAs Influence Promoter Usage of Their Counterpart Sense Genes in Cancer. (Cancer Res, Dec 2021)"},"content":{"rendered":"<p><span class=\"authors-list-item \">Fernando Bellido Molias<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Andre Sim<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Ka Wai Leong<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Omer An<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Yangyang Song<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Vanessa Hui En Ng<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Max Wei Jie Lim<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Chen Ying<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Jasmin Xin Jia Teo<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Jonathan G\u00f6ke<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>3<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Leilei Chen<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>4<span class=\"author-sup-separator\">\u00a0<\/span>5<span class=\"author-sup-separator\">\u00a0<\/span>6<\/sup><\/span><\/p>\n<p class=\"title\"><strong>Affiliations<\/strong><\/p>\n<p><sup class=\"key\">1<\/sup>Cancer Science Institute of Singapore, National University of Singapore, Singapore.<br \/>\n<sup class=\"key\">2<\/sup>Computational and Systems Biology, Genome Institute of Singapore, Singapore.<br \/>\n<sup class=\"key\">3<\/sup>Computational and Systems Biology, Genome Institute of Singapore, Singapore. polly_chen@nus.edu.sg gokej@gis.a-star.edu.sg.<br \/>\n<sup class=\"key\">4<\/sup>Cancer Science Institute of Singapore, National University of Singapore, Singapore. polly_chen@nus.edu.sg gokej@gis.a-star.edu.sg.<br \/>\n<sup class=\"key\">5<\/sup>Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.<br \/>\n<sup class=\"key\">6<\/sup>NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University Singapore, Singapore.<\/p>\n<div id=\"abstract\" class=\"abstract\">\n<p class=\"title\"><strong>Abstract<\/strong><\/p>\n<div id=\"enc-abstract\" class=\"abstract-content selected\">\n<p>Multiple noncoding natural antisense transcripts (ncNAT) are known to modulate key biological events such as cell growth or differentiation. However, the actual impact of ncNATs on cancer progression remains largely unknown. In this study, we identified a complete list of differentially expressed ncNATs in hepatocellular carcinoma. Among them, a previously undescribed ncNAT\u00a0<i>HNF4A-AS1L<\/i>\u00a0suppressed cancer cell growth by regulating its sense gene\u00a0<i>HNF4A<\/i>, a well-known cancer driver, through a promoter-specific mechanism.\u00a0<i>HNF4A-AS1L<\/i>\u00a0selectively activated the\u00a0<i>HNF4A<\/i>\u00a0P1 promoter via HNF1A, which upregulated expression of tumor suppressor P1-driven isoforms, while having no effect on the oncogenic P2 promoter. RNA-seq data from 23 tissue and cancer types identified approximately 100 ncNATs whose expression correlated specifically with the activity of one promoter of their associated sense gene. Silencing of two of these ncNATs\u00a0<i>ENSG00000259357<\/i>\u00a0and\u00a0<i>ENSG00000255031<\/i>\u00a0(antisense to\u00a0<i>CERS2<\/i>\u00a0and\u00a0<i>CHKA<\/i>, respectively) altered the promoter usage of\u00a0<i>CERS2<\/i>\u00a0and\u00a0<i>CHKA<\/i>. Altogether, these results demonstrate that promoter-specific regulation is a mechanism used by ncNATs for context-specific control of alternative isoform expression of their counterpart sense genes. SIGNIFICANCE: This study characterizes a previously unexplored role of ncNATs in regulation of isoform expression of associated sense genes, highlighting a mechanism of alternative promoter usage in cancer.<\/p>\n<\/div>\n<\/div>\n<p class=\"copyright\">\u00a92021 The Authors; Published by the American Association for Cancer Research.<\/p>\n<p class=\"copyright\"><span class=\"id-label\">PMID: <\/span><strong class=\"current-id\" title=\"PubMed ID\">34649947 <\/strong><span class=\"id-label\">DOI:\u00a0<\/span><a class=\"id-link\" href=\"https:\/\/doi.org\/10.1158\/0008-5472.can-21-1859\" target=\"_blank\" rel=\"noopener noreferrer\" data-ga-category=\"full_text\" data-ga-action=\"DOI\">10.1158\/0008-5472.CAN-21-1859<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Fernando Bellido Molias\u00a01,\u00a0Andre Sim\u00a02,\u00a0Ka Wai Leong\u00a01,\u00a0Omer An\u00a01,\u00a0Yangyang Song\u00a01,\u00a0Vanessa Hui En Ng\u00a01,\u00a0Max Wei Jie Lim\u00a01,\u00a0Chen Ying\u00a02,\u00a0Jasmin Xin Jia Teo\u00a01,\u00a0Jonathan G\u00f6ke\u00a03,\u00a0Leilei Chen\u00a04\u00a05\u00a06 Affiliations 1Cancer Science Institute of Singapore, National University of Singapore, &hellip;<\/p>\n<p class=\"read-more\"> <a class=\"\" href=\"https:\/\/csi.nus.edu.sg\/antisense-rnas-influence-promoter-usage-of-their-counterpart-sense-genes-in-cancer-cancer-res-dec-2021\/\"> <span class=\"screen-reader-text\">Antisense RNAs Influence Promoter Usage of Their Counterpart Sense Genes in Cancer. (Cancer Res, Dec 2021)<\/span> Read More &raquo;<\/a><\/p>\n","protected":false},"author":1,"featured_media":32669,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"default","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"","footnotes":""},"categories":[46,16,23],"tags":[],"class_list":["post-33410","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-46","category-latest-happenings","category-research"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.6 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Antisense RNAs Influence Promoter Usage of Their Counterpart Sense Genes in Cancer. 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(Cancer Res, Dec 2021) - NUS CSI\" \/>\n<meta property=\"og:description\" content=\"Fernando Bellido Molias\u00a01,\u00a0Andre Sim\u00a02,\u00a0Ka Wai Leong\u00a01,\u00a0Omer An\u00a01,\u00a0Yangyang Song\u00a01,\u00a0Vanessa Hui En Ng\u00a01,\u00a0Max Wei Jie Lim\u00a01,\u00a0Chen Ying\u00a02,\u00a0Jasmin Xin Jia Teo\u00a01,\u00a0Jonathan G\u00f6ke\u00a03,\u00a0Leilei Chen\u00a04\u00a05\u00a06 Affiliations 1Cancer Science Institute of Singapore, National University of Singapore, &hellip; Antisense RNAs Influence Promoter Usage of Their Counterpart Sense Genes in Cancer. 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