Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer

Su, Wenyu; Li, Jiong-Tang; Cui, Yun; Hong, Jie; Du, Wei; Wang, Yingchao; Lin, Yanwei; Xiong, Hua; Wang, Jilin; Kong, Xuan; Gao, Qin-Yan; Wei, Liping; Fang, Jing‐Yuan

doi:10.1038/cr.2012.57

“…Such sense and antisense transcripts can form dsRNA (Faghihi et al, 2008; Su et al, 2012). Interestingly for TykNu there was a 6.69-fold increase of env-Fc2 antisense transcript levels compared to the sense transcript (Figure 5c) but substantially lower antisense transcripts were seen in both HCT116 and DKO cells (Figures 5c, 6a).…”

Section: Resultsmentioning

confidence: 99%

Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses

Chiappinelli

¹

,

Strissel

²

,

Desrichard

³

et al. 2015

Cell

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Summary We show that DNA methyltransferase inhibitors (DNMTis) upregulate immune signaling in cancer through the viral defense pathway. In ovarian cancer (OC), DNMTis trigger cytosolic sensing of double-stranded RNA (dsRNA) causing a Type I Interferon response and apoptosis. Knocking down dsRNA sensors TLR3 and MAVS reduces this response twofold, and blocking interferon beta or its receptor abrogates it. Upregulation of hypermethylated endogenous retrovirus (ERV) genes accompanies the response and ERV overexpression activates the response. Basal levels of ERV and viral defense gene expression significantly correlate in primary OC and the latter signature separates primary samples for multiple tumor types from The Cancer Genome Atlas into low versus high expression groups. In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.

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“…Table S2), analyzed by the TAG-aided sense/antisense transcript detection (TASA-TD) technique (Henke et al, 2015). Such sense and antisense transcripts can form dsRNA (Faghihi et al, 2008;Su et al, 2012). Interestingly for TykNu there was a 6.69-fold increase of env-Fc2 antisense transcript levels compared to the sense transcript ( Figure 5c) but substantially lower antisense transcripts were seen in both HCT116 and DKO cells (Figures 5c, 6a).…”

Section: Aza-induced Human Endogenous Retrovirus (Erv) Transcripts Camentioning

confidence: 99%

Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses

Chiappinelli¹,

Strissel²,

Desrichard³

et al. 2017

Cell

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SummaryWe show that DNA methyltransferase inhibitors (DNMTis) upregulate immune signaling in cancer through the viral defense pathway. In ovarian cancer (OC), DNMTis trigger cytosolic sensing of double-stranded RNA (dsRNA) causing a Type I Interferon response and apoptosis. Knocking down dsRNA sensors TLR3 and MAVS reduces this response twofold, and blocking interferon beta or its receptor abrogates it. Upregulation of hypermethylated endogenous retrovirus (ERV) genes accompanies the response and ERV overexpression activates the response. Basal levels of ERV and viral defense gene expression significantly correlate in primary OC and the latter signature separates primary samples for multiple tumor types from The Cancer Genome Correspondence should be addressed to Reiner.Strick@uk-erlangen.de and sbaylin@jhmi.edu.. 7 Co-first authors. 8 Co-senior authors.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Author Contributions KBC, PLS, AD, TM, JW, TAC, SBB, and RS designed experiments, performed data analyses, and wrote the manuscript. KBC, PLS, CH, AD, AH, BA, and SB performed experiments. NSR provided ERV-3 env cDNA plasmid and DS provided ovarian cancer cell lines. HL, AS, VM, DMP, LMC, MWB, and CAZ assisted with data analyses. TM, TAC, SBB, and RS contributed equally to this work and are co-senior authors. HHS Public Access

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“…Local cis-regulation involves epigenetic changes proximal to a target gene, whereas distal cis-regulation involves RNA-RNA interactions between transcripts originating from the same locus. Cis-regulation of NATs can lead to activation (Sessa et al 2007;Zhang et al 2009) or silencing (Modarresi et al 2012) of the corresponding sense mRNAs via transcriptional activation (Sessa et al 2007;Zhang et al 2009), silencing (Yu et al 2008;Congrains et al 2013), mRNA stabilization (Mahmoudi et al 2009;Su et al 2012), alternative splicing (Morrissy et al 2011), or post-translational regulation among others. The role of dysregulated antisense transcript expression has been investigated in neurological illnesses such as Alzheimer's disease (Faghihi et al 2008), schizophrenia (Millar et al 2000), Parkinson's disease (Scheele et al 2007), and in multiple cancers (Luo et al 2006;Huarte et al 2010;Geng et al 2011;Kogo et al 2011;Prensner et al 2011;Schmidt et al 2011;Silva et al 2011;Niinuma et al 2012;Han et al 2013;Kim et al 2013b).…”

mentioning

confidence: 99%

The landscape of antisense gene expression in human cancers

Balbin

¹

,

Malik

²

,

Dhanasekaran

³

et al. 2015

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High-throughput RNA sequencing has revealed more pervasive transcription of the human genome than previously anticipated. However, the extent of natural antisense transcripts' (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNAseq) data from 376 cancer samples covering nine tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigation of sense/antisense pair expressions across tissue types revealed lineagespecific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide OncoNAT, a catalog of cancer-related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using OncoNAT we identified several functional NATs, including NKX2-1-AS1 that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs' regulation of tumor suppressors and oncogenes in cancer biology.

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Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer

Cited by 68 publications

References 49 publications

Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses

Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses

Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses

The landscape of antisense gene expression in human cancers

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