Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice.
Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice.
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作者：
Fleming JL;Gable DL;Samadzadeh-Tarighat S;Cheng L;Yu L;Gillespie JL;Toland AE
与小家鼠相比，小家鼠对几种类型的癌症具有高度抗性。为了确定microRNA（miRNA）表达的差异是否解释了菌株之间观察到的皮肤癌易感性的一些差异，我们对超过300种miRNA进行了皮肤RNA的miRNA表达谱分析。通过阵列和/或qPCR，5种miRNAs（miR-1、miR-124 a-3、miR-133 a、miR-134、miR-206）差异表达。miR-1以前被证明在多种肿瘤类型中具有肿瘤抑制能力。我们发现，与正常皮肤相比，小鼠皮肤鳞状细胞癌（cSCC）中的miR-1表达较低。基于文献和我们的表达数据，我们对预测的miR-1靶点进行了详细的研究，并评估了miR-1表达对两种小鼠cSCC细胞系A5和B 9的影响。在转染miR-1后，我们发现三个经验证的miR-1靶点Met、Twf 1和Ets 1以及一个新靶点Bag 4的mRNA表达降低。通过Western分析和含有野生型和突变的Ets 1 3 'UTR的3'报告荧光素酶测定证实Ets 1的表达降低。我们评估了miR-1对多种肿瘤表型的影响，包括凋亡、增殖、细胞周期和迁移。在A5细胞中，与对照miR相比，miR-1的表达导致增殖降低。miR-1的表达也导致细胞凋亡增加，在稍后的时间点（72和96小时），并在S期细胞减少。总之，我们鉴定了5种在癌症抗性和癌症易感小鼠之间具有差异表达的miRNAs，并发现miR-1，一种候选肿瘤抑制因子，具有在肿瘤发生中具有确定作用的靶点。
Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA) expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs) compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3’ reporter luciferase assays containing wildtype and mutated Ets1 3’UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h) and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis.
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影响因子：
8
作者：
Hahne, JC;Okuducu, AF;Wernert, N
通讯作者：
Wernert, N
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
14.9
作者：
Hudson RS;Yi M;Esposito D;Watkins SK;Hurwitz AA;Yfantis HG;Lee DH;Borin JF;Naslund MJ;Alexander RB;Dorsey TH;Stephens RM;Croce CM;Ambs S
通讯作者：
Ambs S
DOI：
10.1073/pnas.0403293101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Liu, CG;Calin, GA;Croce, CM
通讯作者：
Croce, CM
影响因子：
3.3
作者：
Huang, Hanwen;Eversley, Chevonne D.;Zou, Fei
通讯作者：
Zou, Fei