Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.
Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.
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DOI：
10.1371/journal.pone.0071969
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Koike K
中科院分区：
文献类型：
--
作者：
Yoshikawa T;Otsuka M;Kishikawa T;Takata A;Ohno M;Shibata C;Kang YJ;Yoshida H;Koike K
在人类癌症中通常观察到microRNA（miRNAs）的广泛下调表达。类似地，导致整体miRNA表达减少的miRNA加工途径组分的表达失调也可能与肿瘤发生相关。在这里，我们表明，特异性消融肠上皮细胞中的Dicer1加速肠道炎症相关的肿瘤发生。这种效应仅在Dicer1的单拷贝缺失时才明显，但在Dicer1完全缺失时则不明显。Dicer表达和随后的成熟miRNA水平与完整Dicer1等位基因的数量呈负相关。由于Dicer的表达水平在肿瘤及其周围组织中保留，即使在诱导结肠炎相关肿瘤后，Dicer 1缺失的影响是细胞自主的。虽然在大多数情况下，代表性癌基因和肿瘤抑制基因的表达水平与DICER的表达水平呈负相关，但有些基因不受DICER 1缺失的影响。因此，解除调节肿瘤促进和抑制基因的表达水平之间的微妙平衡可能是至关重要的肿瘤发生在这种独特的单倍不足的情况下。
A widespread downregulated expression of microRNAs (miRNAs) is commonly observed in human cancers. Similarly, deregulated expression of miRNA-processing pathway components, which results in the reduction of global miRNA expression, may also be associated with tumorigenesis. Here, we show that specific ablation of Dicer1 in intestinal epithelial cells accelerates intestinal inflammation-associated tumorigenesis. This effect was apparent only when a single copy of Dicer1 was deleted, but not with complete Dicer1 ablation. DICER expression and subsequent mature miRNA levels were inversely correlated with the number of intact Dicer1 alleles. Because the expression levels of DICER were retained in tumors and its surrounding tissues even after induction of colitis-associated tumors, the effects of Dicer1 deletion were cell-autonomous. Although the expression levels of representative oncogenes and tumor suppressor genes were in most cases inversely correlated with the expression levels of DICER, some genes were not affected by Dicer1 deletion. Thus, deregulating the delicate balance between the expression levels of tumor-promoting and -suppressive genes may be crucial for tumorigenesis in this unique haploinsufficient case.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
29.4
作者：
McKenna LB;Schug J;Vourekas A;McKenna JB;Bramswig NC;Friedman JR;Kaestner KH
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Kaestner KH
影响因子：
12.4
作者：
Lambertz, I.;Nittner, D.;Mestdagh, P.;Denecker, G.;Vandesompele, J.;Dyer, M. A.;Marine, J-C
通讯作者：
Marine, J-C
影响因子：
29.4
作者：
Otsuka M;Kang YJ;Ren J;Jiang H;Wang Y;Omata M;Han J
通讯作者：
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DOI：
10.1126/science.1174334
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hill DA;Ivanovich J;Priest JR;Gurnett CA;Dehner LP;Desruisseau D;Jarzembowski JA;Wikenheiser-Brokamp KA;Suarez BK;Whelan AJ;Williams G;Bracamontes D;Messinger Y;Goodfellow PJ
通讯作者：
Goodfellow PJ