首页> 外文期刊>RNA biology >SRSF3 and hnRNP H1 regulate a splicing hotspot of HER2 in breast cancer cells
【24h】

SRSF3 and hnRNP H1 regulate a splicing hotspot of HER2 in breast cancer cells

机译:SRSF3和hnRNP H1调节乳腺癌细胞中HER2的剪接热点

获取原文
获取原文并翻译 | 示例
获取外文期刊封面目录资料

摘要

Overexpression of the oncogene HER2 occurs in 20-30% of invasive breast cancer and is associated with poor prognosis. A number of different splice variants of HER2 have been identified which produce functionally different proteins. Previously these splice variants have been investigated separately, but in the present study we collectively look at the expression and regulation of a group of HER2 splice variants produced by a splicing hotspot. Initial investigation in a cohort of tumor samples showed large variations in HER2 variant expression between patient samples. RNA interference studies identified 2 splicing factors involved in the regulation of splicing within this region, hnRNP H1 and SRSF3. siRNA targeting hnRNP H1 increases levels of X5 and the oncogenic variant 16HER2. Furthermore RNA chromatography assays demonstrated binding of hnRNP H1 to RNA in this region. Additionally the proto-oncogene SRSF3 was also identified as an important regulator of splicing with SRSF3 knockdown resulting in changes in all the splice variants located at the hotspot. Most notably knockdown of SRSF3 resulted in a switch from the oncogenic 16HER2 to p100 which inhibits cell proliferation. Binding of SRSF3 to RNA within this region was also demonstrated by RNA chromatography and more specifically 2 SRSF3 binding sites were identified within exon 15. SRSF3 and hnRNP H1 are the first splicing factors identified which regulate the production of these functionally distinct HER2 splice variants and therefore maybe important for the regulation of HER2 signaling.
机译:癌基因HER2的过度表达发生在20-30%的浸润性乳腺癌中,并与不良预后相关。已经鉴定出产生功能上不同的蛋白质的许多不同的HER2剪接变体。以前已经分别研究了这些剪接变体,但是在本研究中,我们共同研究了由剪接热点产生的一组HER2剪接变体的表达和调控。对一组肿瘤样品的初步研究表明,患者样品之间HER2变异体表达存在较大差异。 RNA干扰研究确定了涉及该区域内剪接调控的2个剪接因子,hnRNP H1和SRSF3。靶向hnRNP H1的siRNA增加X5和致癌变体16HER2的水平。此外,RNA色谱分析表明hnRNP H1与该区域的RNA结合。另外,原癌基因SRSF3也被认为是剪接SRSF3的重要调控因子,导致位于热点的所有剪接变体发生变化。最值得注意的是,SRSF3的敲低导致从致癌的16HER2到抑制细胞增殖的p100的转换。 RNA层析还证实了SRSF3与该区域内RNA的结合,更具体地说,在第15外显子中鉴定出2个SRSF3结合位点。SRSF3和hnRNP H1是首先鉴定的调节这些功能不同的HER2剪接变体产生的剪接因子,因此可能对HER2信号的调控很重要。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号