MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment.
MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment.
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DOI：
10.1038/ncomms13597
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发表时间：
2016-11-25
影响因子：
16.6
通讯作者：
Anand, Sudarshan
中科院分区：
文献类型：
--
作者：
Wilson, RaeAnna;Espinosa-Diez, Cristina;Kanner, Nathan;Chatterjee, Namita;Ruhl, Rebecca;Hipfinger, Christina;Advani, Sunil J.;Li, Jie;Khan, Omar F.;Franovic, Aleksandra;Weis, Sara M.;Kumar, Sushil;Coussens, Lisa M.;Anderson, Daniel G.;Chen, Clark C.;Cheresh, David A.;Anand, Sudarshan
不是直接靶向肿瘤细胞，而是可以调节肿瘤微环境的元素以使肿瘤对治疗效果敏感。在这里，我们报告了一种独特的机制，异位microRNA-103可以操纵肿瘤相关的内皮细胞，以增强肿瘤细胞死亡。使用功能获得和丧失方法，我们表明miR-103在体外和体内加剧DNA损伤并抑制血管生成。在荷瘤小鼠中局部、全身或血管靶向递送miR-103可降低血管生成和肿瘤生长。从机制上讲，miR-103在内皮细胞中对其靶基因TREX 1的调节控制促炎细胞因子分泌到肿瘤微环境中。我们的数据表明，这种炎症环境可能通过支持免疫激活和诱导Fas和TRAIL受体的肿瘤表达来增强肿瘤细胞死亡。我们的研究结果揭示了miR介导的血管和肿瘤细胞之间的串扰，可以用来提高化疗和放疗的疗效。 可以调节肿瘤微环境以使肿瘤对治疗效果敏感。在这里，作者表明辐射诱导的miR-103下调内皮细胞中的TREX 1，减少血管生成，并导致促炎介质的分泌，从而减少肿瘤生长。
Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth. Mechanistically, miR-103 regulation of its target gene TREX1 in endothelial cells governs the secretion of pro-inflammatory cytokines into the tumour microenvironment. Our data suggest that this inflammatory milieu may potentiate tumour cell death by supporting immune activation and inducing tumour expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk between vasculature and tumour cells that can be exploited to improve the efficacy of chemotherapy and radiation. The tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here the authors show that radiation induced miR-103 downregulates TREX1 in endothelial cells, decreases angiogenesis and leads to the secretion of proinflammatory mediators that reduce tumour growth.
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影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
4.3
作者：
Kavanagh, David;Spitzer, Dirk;Atkinson, John P.
通讯作者：
Atkinson, John P.
DOI：
10.1073/pnas.1218887109
发表时间：
2012-12-11
影响因子：
11.1
作者：
Cambronne, Xiaolu A.;Shen, Rongkun;Goodman, Richard H.
通讯作者：
Goodman, Richard H.
影响因子：
20.1
作者：
Bodnar, RJ;Yates, CC;Wells, A
通讯作者：
Wells, A
DOI：
10.1084/jem.182.1.155
发表时间：
1995-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Angiolillo AL;Sgadari C;Taub DD;Liao F;Farber JM;Maheshwari S;Kleinman HK;Reaman GH;Tosato G
通讯作者：
Tosato G