The landscape of antisense gene expression in human cancers.
The landscape of antisense gene expression in human cancers.
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DOI：
10.1101/gr.180596.114
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发表时间：
2015-07
期刊：
影响因子：
7
通讯作者：
Chinnaiyan AM
中科院分区：
文献类型：
--
作者：
Balbin OA;Malik R;Dhanasekaran SM;Prensner JR;Cao X;Wu YM;Robinson D;Wang R;Chen G;Beer DG;Nesvizhskii AI;Chinnaiyan AM
高通量RNA测序揭示了比先前预期更普遍的人类基因组转录。然而，自然反义转录本(NAT)的表达程度、它们对同源正义基因的调控以及NAT在癌症中的作用仍然知之甚少。在这里，我们使用来自涵盖9种组织类型的376个癌症样本的链特异性配对末端RNA测序(ssRNA-seq)数据来全面描述反义表达的图景。我们发现在至少38%的带注释的转录本中有一致的反义表达，这通常与正义基因的表达呈正相关。对不同组织类型的正义/反义对表达的研究揭示了谱系特异的、普遍存在的和癌症特异的反义基因转录。肿瘤和正常样本之间的比较确定了一致(相同方向)和不一致(相反方向)正义/反义表达模式。最后，我们提供了OncoNAT，这是一个具有显著反义转录的癌症相关基因目录，这将使未来研究癌症中的正义/反义调控成为可能。利用OncoNAT，我们鉴定了几个具有功能的NAT，包括调节肺癌细胞中NKX2-1癌基因和细胞增殖的NKX2-1-AS1。总体而言，这项研究提供了对NAT的全面描述，并支持NAT在癌症生物学中对肿瘤抑制基因和癌基因的调节作用。
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 (ssRNA-seq) 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 lineage-specific, 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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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
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Rinn JL
影响因子：
14.9
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Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
影响因子：
4.8
作者：
Michael, Daryn R.;Phillips, Aled O.;Bowen, Timothy
通讯作者：
Bowen, Timothy