Identification of a new target of miR-16, Vacuolar Protein Sorting 4a.
Identification of a new target of miR-16, Vacuolar Protein Sorting 4a.
复制标题
DOI：
10.1371/journal.pone.0101509
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hall JL
中科院分区：
文献类型：
--
作者：
Adhikari N;Guan W;Capaldo B;Mackey AJ;Carlson M;Ramakrishnan S;Walek D;Gupta M;Mitchell A;Eckman P;John R;Ashley E;Barton PJ;Hall JL
其基本原理是利用生物信息学方法识别具有单核苷酸突变(SNPs)的基因中的miRNA结合部位，以发现心力衰竭(HF)的通路。其目的是集中于包含miRNA结合位点的基因，这些miRNA与miRNAs在终末期心力衰竭和左心室辅助装置(LVAD)的反应中发生显著变化。使用BEDTools v2.14.3来区分预测的3‘UTRmiRNA结合位点内的SNP。作为MIR-15/107家族的一员，MIR-16在终末期心力衰竭患者的循环中减少，并在左心衰的反应中增加(p<；0.001)。MIR-16降低HEK 293T细胞空泡蛋白分选4a(VPS4a)的表达(P<0.01)。在VPS4a的miR-15/107家族结合位点上发现了SNP rs16958754，取消了miR-16与VPS4a的3‘非编码区的直接结合(p<；0.05)。终末期心衰患者循环中VPS4a增多(P<；0.001)，体外HEK293T细胞数量减少(P<；0.001)。我们提供的证据表明，miR-16在终末期心力衰竭患者的循环中减少，并随着LVAD的增加而增加。模型研究表明miR-16与VPS4a结合并减少VPS4a的表达。过表达VPS4a使细胞数减少。综上所述，这些实验表明miR-16和VPS4a的表达在终末期心力衰竭和左心室反搏的反应中发生了变化。这一信号通路可能导致心力衰竭患者循环细胞数量减少。
The rationale was to utilize a bioinformatics approach to identify miRNA binding sites in genes with single nucleotide mutations (SNPs) to discover pathways in heart failure (HF). The objective was to focus on the genes containing miRNA binding sites with miRNAs that were significantly altered in end-stage HF and in response to a left ventricular assist device (LVAD). BEDTools v2.14.3 was used to discriminate SNPs within predicted 3′UTR miRNA binding sites. A member of the miR-15/107 family, miR-16, was decreased in the circulation of end-stage HF patients and increased in response to a LVAD (p<0.001). MiR-16 decreased Vacuolar Protein Sorting 4a (VPS4a) expression in HEK 293T cells (p<0.01). The SNP rs16958754 was identified in the miR-15/107 family binding site of VPS4a which abolished direct binding of miR-16 to the 3′UTR of VPS4a (p<0.05). VPS4a was increased in the circulation of end-stage HF patients (p<0.001), and led to a decrease in the number of HEK 293T cells in vitro (p<0.001). We provide evidence that miR-16 decreases in the circulation of end-stage HF patients and increases with a LVAD. Modeling studies suggest that miR-16 binds to and decreases expression of VPS4a. Overexpression of VPS4a decreases cell number. Together, these experiments suggest that miR-16 and VPS4a expression are altered in end-stage HF and in response to unloading with a LVAD. This signaling pathway may lead to reduced circulating cell number in HF.
登录
查看更多内容
影响因子：
5.6
作者：
Finnerty JR;Wang WX;Hébert SS;Wilfred BR;Mao G;Nelson PT
通讯作者：
Nelson PT
影响因子：
9
作者：
通讯作者：
--
影响因子：
--
作者：
Corsten, Maarten F.;Dennert, Robert;Schroen, Blanche
通讯作者：
Schroen, Blanche
DOI：
10.1161/atvbaha.111.226696
发表时间：
2011-11-01
影响因子：
8.7
作者：
Fichtlscherer, Stephan;Zeiher, Andreas M.;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
16
作者：
Rissland OS;Hong SJ;Bartel DP
通讯作者：
Bartel DP