Snijders Antoine M, Mao Jian-Hua
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Insights Cancer Res. 2016;1:1-5. Epub 2016 Apr 30.
an E3-ubiquitin protein ligase in SCFs (SKP1-cullin-F-box) complex, is a major human tumor suppressor gene, and understanding mechanisms by which FBXW7 contributes to tumorigenesis is critical for the treatment of human cancers with deficiency. Long non-coding RNAs (lncRNAs) have emerged as key regulators of various biological processes. Here we have identified a set of lncRNAs that are associated with Fbxw7 deficiency. The correlation network and functional annotation analysis revealed that Fbxw7-associated lncRNAs regulate genes involved in cell cycle, DNA repair, metabolic process, and cell communication and adhesion. The number of coding genes that correlated with individual lncRNAs varied largely. A lncRNA on chromosome 15 (A_30_P01032978), which was upregulated in tumors from Fbxw7 deficient mice was positively correlated with 15 coding genes. High expression of this 15-gene signature was associated with poor prognosis in two independent human breast cancer studies. Our results open possible new avenues to understand mechanisms by which Fbxw7 deficiency increases tumor susceptibility via the alteration of lncRNAs.
作为SCF（SKP1-泛素连接酶-Cullin-F盒）复合物中的一种E3泛素蛋白连接酶，是一种主要的人类肿瘤抑制基因，了解FBXW7促进肿瘤发生的机制对于治疗存在缺陷的人类癌症至关重要。长链非编码RNA（lncRNA）已成为各种生物过程的关键调节因子。在此，我们鉴定出了一组与Fbxw7缺陷相关的lncRNA。相关网络和功能注释分析表明，与Fbxw7相关的lncRNA调节参与细胞周期、DNA修复、代谢过程以及细胞通讯和黏附的基因。与单个lncRNA相关的编码基因数量差异很大。在Fbxw7缺陷小鼠的肿瘤中上调的位于15号染色体上的一个lncRNA（A_30_P01032978）与15个编码基因呈正相关。在两项独立的人类乳腺癌研究中，这种15基因特征的高表达与预后不良相关。我们的研究结果为理解Fbxw7缺陷通过lncRNA改变增加肿瘤易感性的机制开辟了可能的新途径。
