Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer.
Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer.
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DOI：
10.1016/j.ebiom.2022.104319
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发表时间：
2022-11
期刊：
影响因子：
11.1
通讯作者：
Cui, Jie
中科院分区：
文献类型：
--
作者：
Wang, Jinghan;Ren, Meng;Yu, Jundan;Hu, Mingtai;Wang, Xiaojing;Ma, Wencong;Jiang, Xiaoqing;Cui, Jie
关键词：
胆囊癌（GBC）是最常见的胆道恶性肿瘤，诊断晚，生存率低，需要不断寻找新的诊断标志物和治疗靶点。人内源性逆转录病毒（HERV）特别容易在各种癌症中被重新激活，并与癌症进展和免疫治疗有关。对来自4名GBC患者的肿瘤组织和配对的邻近组织进行单细胞RNA测序。应用双荧光素酶报告基因测定来测量HERV序列的增强子活性。我们剖析了细胞的多样性，并描述了GBC的HERV转录组景观。我们发现HERV以细胞类型特异性的方式转录，并且不同的HERV家族与不同的生物学效应相关。HERV可以充当增强子，推测会导致邻近基因的表达改变。HERVH的转录水平随着上皮细胞恶性转化而逐渐升高，提示HERVH可能是GBC的一个潜在的早期诊断生物标志物。HHLA 2是一种新出现的免疫检查点，由HERVH衍生，与HERVH表达相关，被认为是一种有前途的免疫治疗靶点。探索HERVs的转录格局和潜在功能影响突出了HERVs在GBC中的重要作用，并为管理GBC提供了新的视角。本研究得到了国家自然科学基金（31970176，81972256）和江苏省创新能力建设项目（BM 2020019）的资助。
Gallbladder cancer (GBC), the most common malignancy of the biliary tract, shows late diagnosis and low survival rate and requires continued search for new diagnostic biomarkers and therapeutic targets. Human endogenous retroviruses (HERVs) are specifically prone to be reactivated in diverse cancers and are implicated in cancer progression and immunotherapy. Single-cell RNA sequencing was performed on tumor tissues and paired adjacent tissues from 4 GBC patients. Dual-luciferase reporter assay was applied to measure enhancer activity of HERV sequences. We dissected the cellular diversity and described the HERV transcriptomic landscape for GBC. We found that HERVs were transcribed in a cell type-specific manner and different HERV families were associated with diverse biological effects. HERVs could function as enhancers, presumably causing altered expression of neighboring genes. The transcription level of HERVH was gradually elevated with the malignant transformation of epithelial cells, suggesting HERVH may be a potential early diagnostic biomarker of GBC. HHLA2, a newly emerging immune checkpoint, was derived by HERVH, exhibited an expressional correlation with HERVH, and was identified as a promising target for immunotherapy. Exploring the transcriptional landscape and potential functional impact of HERVs highlights the important role of HERVs in GBC and provides a fresh perspective on managing GBC. This study was supported by the National Natural Science Foundation of China (31970176, 81972256) and the research grants from the Innovation Capacity Building Project of Jiangsu province (BM2020019).
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影响因子：
13.6
作者：
Ito J;Kimura I;Soper A;Coudray A;Koyanagi Y;Nakaoka H;Inoue I;Turelli P;Trono D;Sato K
通讯作者：
Sato K
影响因子：
50.3
作者：
Hornburg, Milena;Desbois, Melanie;Wang, Yulei
通讯作者：
Wang, Yulei
DOI：
10.1126/science.aad5497
发表时间：
2016-03-04
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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影响因子：
4.4
作者：
Chow, Kevin V.;Lew, Andrew M.;Zhan, Yifan
通讯作者：
Zhan, Yifan
DOI：
10.1093/database/bax028
发表时间：
2017-01-01
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Fishilevich S;Nudel R;Rappaport N;Hadar R;Plaschkes I;Iny Stein T;Rosen N;Kohn A;Twik M;Safran M;Lancet D;Cohen D
通讯作者：
Cohen D