PAN-cancer analysis of S-phase enriched lncRNAs identifies oncogenic drivers and biomarkers.
PAN-cancer analysis of S-phase enriched lncRNAs identifies oncogenic drivers and biomarkers.
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DOI：
10.1038/s41467-018-03265-1
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发表时间：
2018-02-28
影响因子：
16.6
通讯作者：
Kanduri C
中科院分区：
文献类型：
--
作者：
Ali MM;Akhade VS;Kosalai ST;Subhash S;Statello L;Meryet-Figuiere M;Abrahamsson J;Mondal T;Kanduri C
尽管我们对长非编码RNA(LncRNAs)在癌症中的作用有了更深入的了解，但寻找与临床相关的癌症相关LncRNAs的努力仍然不足。在这里，使用新生RNA捕获测序，我们鉴定了1145个时间表达的S阶段丰富的lncRNAs。其中，570个LncRNA在TCGA数据集的至少一种肿瘤类型中显示出显著的差异表达。对14个泛癌数据集的系统临床研究确定了633个独立的预后标记物。在几种癌症模型中，沉默顶级差异表达和临床相关的S期丰富的lncRNA会影响关键的癌细胞特征。SCAT7在多种肿瘤类型中的机制研究表明，它与hnRNPK/YBX1复合体相互作用，并通过调节成纤维细胞生长因子/FGFR及其下游的PI3K/AKT和MAPK通路影响癌细胞的标志。我们还实施了一种基于LNA反义寡核苷酸的策略来治疗癌细胞系和患者来源的肿瘤(PDX)异种移植。因此，这项研究提供了一个基于LncRNA的具有潜在预后价值的致癌驱动因素的综合清单。虽然我们知道lncRNAs在癌症中发挥了作用，但对临床上相关的和具有功能的lncRNAs的鉴定还很缺乏。在这里，作者识别了633个预后标志物，570个与S期癌症相关的LncRNA，并表明SCAT7通过与hnRNPK/YBX1复合体相互作用来调节成纤维细胞生长因子/成纤维细胞生长因子受体和PI3K/AKT/MAPK通路。
Despite improvement in our understanding of long noncoding RNAs (lncRNAs) role in cancer, efforts to find clinically relevant cancer-associated lncRNAs are still lacking. Here, using nascent RNA capture sequencing, we identify 1145 temporally expressed S-phase-enriched lncRNAs. Among these, 570 lncRNAs show significant differential expression in at least one tumor type across TCGA data sets. Systematic clinical investigation of 14 Pan-Cancer data sets identified 633 independent prognostic markers. Silencing of the top differentially expressed and clinically relevant S-phase-enriched lncRNAs in several cancer models affects crucial cancer cell hallmarks. Mechanistic investigations on SCAT7 in multiple cancer types reveal that it interacts with hnRNPK/YBX1 complex and affects cancer cell hallmarks through the regulation of FGF/FGFR and its downstream PI3K/AKT and MAPK pathways. We also implement a LNA-antisense oligo-based strategy to treat cancer cell line and patient-derived tumor (PDX) xenografts. Thus, this study provides a comprehensive list of lncRNA-based oncogenic drivers with potential prognostic value. Although we know lncRNAs play a role in cancer, the identification of clinically relevant and functional lncRNAs is lacking. Here, the authors identify 633 prognostic markers, 570 S-phase cancer-associated lncRNAs, and show SCAT7 regulates FGF/FGFR and PI3K/AKT/MAPK pathways via interaction with hnRNPK/YBX1 complexes.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
8.4
作者：
Basaki, Yuji;Taguchi, Ken-ichi;Kuwano, Michihiko
通讯作者：
Kuwano, Michihiko