Hypoxia-Dependent mRNA Expression Pattern of Splicing Factor YT521 and Its Impact on Oncological Important Target Gene Expression
Hypoxia-Dependent mRNA Expression Pattern of Splicing Factor YT521 and Its Impact on Oncological Important Target Gene Expression
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DOI：
10.1002/mc.22045
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发表时间：
2014-11-01
影响因子：
4.6
通讯作者：
Stickeler, Elmar
中科院分区：
文献类型：
--
作者：
Hirschfeld, Marc;Zhang, Bo;Stickeler, Elmar
广泛表达的剪接因子YT521（YTHDC1）的特征在于可变剪接的同种型，其对癌症相关基因表达具有调节影响。我们最近的研究结果解释了YT 521在子宫内膜癌中的预后意义。在这项研究中，我们研究了缺氧依赖性的YT 521表达，以及其差异异构体活性的肿瘤学重要的靶基因。通过特异性靶基因CD44的微基因测定研究了YT 521对剪接的潜在调节影响。分别通过YT521敲低或过表达进行功能性剪接分析。此外，在缺氧条件下测定YT 521的表达。两种产生蛋白质的YT521 mRNA亚型1和2引起相当的、特异性的CD44v选择性剪接诱导（P
The ubiquitously expressed splicing factor YT521 (YTHDC1) is characterized by alternatively spliced isoforms with regulatory impact on cancer-associated gene expression. Our recent findings account for the prognostic significance of YT521 in endometrial cancer. In this study, we investigated the hypoxia-dependency of YT521 expression as well as its differential isoform activities on oncological important target genes. YT521's potential regulatory influence on splicing was investigated by a minigene assay for the specific target gene CD44. Functional splicing analysis was performed by YT521 knock-down or overexpression, respectively. In addition, YT521 expression was determined under hypoxia. The two protein-generating YT521 mRNA isoforms 1 and 2 caused a comparable, specific induction of CD44v alternative splicing (P