Thyroid hormone may regulate mRNA abundance in liver by acting on microRNAs.
Thyroid hormone may regulate mRNA abundance in liver by acting on microRNAs.
复制标题
DOI：
10.1371/journal.pone.0012136
复制
发表时间：
2010-08-13
期刊：
影响因子：
3.7
通讯作者：
Yauk C
中科院分区：
文献类型：
--
作者：
Dong H;Paquette M;Williams A;Zoeller RT;Wade M;Yauk C
MicroRNAs （miRNAs）广泛参与多种生物过程。然而，关于mirna在介导甲状腺激素（TH）作用中的作用知之甚少。已知适当的TH水平对哺乳动物的发育、分化和维持代谢平衡至关重要。我们从出生后第12至15天（PND）通过短期暴露于甲巯咪唑和高氯酸盐诱导幼年小鼠短暂性甲状腺功能减退。使用Taqman低密度阵列（包含多达600个啮齿动物mirna）分析肝脏中mirna的表达。我们发现，与甲状腺功能正常的对照组相比，甲状腺功能减退小鼠肝脏中40种mirna的表达显著改变。其中，mirna -1、206、133a和133b的表达量大幅增加（50- 500倍）。在多种小鼠模型中，包括慢性甲状腺功能减退、短期甲状腺功能亢进和短期甲状腺功能减退后补充甲状腺激素，证实了甲状腺激素对mir -1、206、133a和133b表达的调节作用。在小鼠肝细胞AML - 12细胞中也证实了TH对这些mirna的调控。在AML 12细胞中检测mir-1、206、133a和133b的前体表达，经TH处理后，mir-1、206、133a和133b的表达均下降，只有pre-mir-206和pre-mir-133b具有统计学意义。为了确定这些mirna的靶点，研究人员使用DNA微阵列检测短期甲状腺功能减退小鼠模型中相对于对照组的肝脏mRNA水平。我们发现，在这些甲状腺功能减退的小鼠中，92个已知基因的转录本发生了显著改变。基于网络的靶标预测软件（TargetScan和microcosmos）鉴定出其中14个转录本是mir -1、206、133a和133b的靶标。这些mRNA靶点绝大多数在甲状腺功能减退小鼠中显著下调，与甲状腺功能减退小鼠肝脏中mir -1、206、133a和133b的上调相对应。为了进一步研究靶基因，miR-206在AML 12细胞中过表达。TH处理过表达miR-206的细胞导致miR-206表达降低，两个预测靶基因Mup1和Gpd2显著增加。结果表明，TH对这些基因的调控可能是通过miR-206继发发生的。这些研究为mirna在介导TH调控基因表达中的作用提供了新的见解。
MicroRNAs (miRNAs) are extensively involved in diverse biological processes. However, very little is known about the role of miRNAs in mediating the action of thyroid hormones (TH). Appropriate TH levels are known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short-term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed using Taqman Low Density Arrays (containing up to 600 rodent miRNAs). We found the expression of 40 miRNAs was significantly altered in the livers of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miRs-1, 206, 133a and 133b exhibited a massive increase in expression (50- to 500-fold). The regulation of TH on the expression of miRs-1, 206, 133a and 133b was confirmed in various mouse models including: chronic hypothyroid, short-term hyperthyroid and short-term hypothyroid followed by TH supplementation. TH regulation of these miRNAs was also confirmed in mouse hepatocyte AML 12 cells. The expression of precursors of miRs-1, 206, 133a and 133b were examined in AML 12 cells and shown to decrease after TH treatment, only pre-mir-206 and pre-mir-133b reached statistical significance. To identify the targets of these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the short-term hypothyroid mouse model relative to controls. We found transcripts from 92 known genes were significantly altered in these hypothyroid mice. Web-based target predication software (TargetScan and Microcosm) identified 14 of these transcripts as targets of miRs-1, 206, 133a and 133b. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding with the up-regulation of miRs-1, 206, 133a and 133b in hypothyroid mouse liver. To further investigate target genes, miR-206 was over-expressed in AML 12 cells. TH treatment of cells over-expressing miR-206 resulted in decreased miR-206 expression, and a significant increase in two predicted target genes, Mup1 and Gpd2. The results suggest that TH regulation of these genes may occur secondarily via miR-206. These studies provide new insight into the role of miRNAs in mediating TH regulation of gene expression.
登录
查看更多内容
影响因子：
3.7
作者：
Logan DW;Marton TF;Stowers L
通讯作者：
Stowers L
影响因子：
4.3
作者：
Chen, Xian-Ming
通讯作者：
Chen, Xian-Ming
DOI：
10.1016/j.jsbmb.2008.06.010
发表时间：
2008-09-01
影响因子：
4.1
作者：
Bryzgalova, Galina;Effendic, Suad;Grover, Gary J.
通讯作者：
Grover, Gary J.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.7
作者：
Guled, Mohamed;Lahti, Leo;Knuutila, Sakari
通讯作者：
Knuutila, Sakari