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Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers.

免疫相关 lncRNAs 的泛癌症表征确定了潜在的致癌生物标志物。

  • 影响因子:12.19
  • DOI:10.1038/s41467-020-14802-2
  • 作者列表:"Li Y","Jiang T","Zhou W","Li J","Li X","Wang Q","Jin X","Yin J","Chen L","Zhang Y","Xu J","Li X
  • 发表时间:2020-02-21
Abstract

:Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and they play fundamental roles in immune regulation. Here we introduce an integrated algorithm, ImmLnc, for identifying lncRNA regulators of immune-related pathways. We comprehensively chart the landscape of lncRNA regulation in the immunome across 33 cancer types and show that cancers with similar tissue origin are likely to share lncRNA immune regulators. Moreover, the immune-related lncRNAs are likely to show expression perturbation in cancer and are significantly correlated with immune cell infiltration. ImmLnc can help prioritize cancer-related lncRNAs and further identify three molecular subtypes (proliferative, intermediate, and immunological) of non-small cell lung cancer. These subtypes are characterized by differences in mutation burden, immune cell infiltration, expression of immunomodulatory genes, response to chemotherapy, and prognosis. In summary, the ImmLnc pipeline and the resulting data serve as a valuable resource for understanding lncRNA function and to advance identification of immunotherapy targets.

摘要

: 长链非编码 rna (Long noncoding RNAs,lncRNAs) 正在成为基因表达的关键调控因子,它们在免疫调节中发挥基本作用。这里我们介绍了一种集成算法 ImmLnc,用于鉴定免疫相关通路的 lncRNA 调控因子。我们全面绘制了 33 种癌症免疫组中 lncRNA 调控的图景,并表明具有相似组织来源的癌症可能共享 lncRNA 免疫调控因子。此外,免疫相关 lncRNAs 很可能在癌症中表现出表达扰动,并与免疫细胞浸润显著相关。Imlnc 可以帮助优先考虑癌症相关 lncRNAs,并进一步鉴定非小细胞肺癌的三种分子亚型 (增殖性、中间性和免疫性)。这些亚型的特点是突变负荷、免疫细胞浸润、免疫调节基因表达、化疗反应和预后的差异。总之,ImmLnc 管道和由此产生的数据作为理解 lncRNA 功能和推进免疫治疗靶点鉴定的宝贵资源。

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影响因子:5.25
发表时间:2020-01-23
DOI:10.1158/1535-7163.MCT-19-0947
作者列表:["Joshi S","Liu KX","Zulcic M","Singh AR","Skola D","Glass CK","Sanders PD","Sharabi AB","Pham TV","Tamayo P","Shiang D","Dinh HQ","Hedrick CC","Morales GA","Garlich JR","Durden DL"]

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关键词: 暂无
翻译标题与摘要 下载文献
影响因子:12.19
发表时间:2020-01-23
来源期刊:Nature communications
DOI:10.1038/s41467-020-14332-x
作者列表:["Fu S","He K","Tian C","Sun H","Zhu C","Bai S","Liu J","Wu Q","Xie D","Yue T","Shen Z","Dai Q","Yu X","Zhu S","Liu G","Zhou R","Duan S","Tian Z","Xu T","Wang H","Bai L"]

METHODS::Dysfunction of invariant natural killer T (iNKT) cells in tumor microenvironment hinders their anti-tumor efficacy, and the underlying mechanisms remain unclear. Here we report that iNKT cells increase lipid biosynthesis after activation, and that is promoted by PPARγ and PLZF synergically through enhancing transcription of Srebf1. Among those lipids, cholesterol is required for the optimal IFN-γ production from iNKT cells. Lactic acid in tumor microenvironment reduces expression of PPARγ in intratumoral iNKT cells and consequently diminishes their cholesterol synthesis and IFN-γ production. Importantly, PPARγ agonist pioglitazone, a thiazolidinedione drug for type 2 diabetes, successfully restores IFN-γ production in tumor-infiltrating iNKT cells from both human patients and mouse models. Combination of pioglitazone and alpha-galactosylceramide treatments significantly enhances iNKT cell-mediated anti-tumor immune responses and prolongs survival of tumor-bearing mice. Our studies provide a strategy to augment the anti-tumor efficacy of iNKT cell-based immunotherapies via promoting their lipid biosynthesis.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:8.58
发表时间:2020-01-17
DOI:10.1158/2326-6066.CIR-19-0517
作者列表:["Maruoka Y","Furusawa A","Okada R","Inagaki F","Fujimura D","Wakiyama H","Kato T","Nagaya T","Choyke PL","Kobayashi H"]

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