缺氧肿瘤细胞中 HIF1A 共因子的系统研究。
A systematic study of HIF1A cofactors in hypoxic cancer cells.
机构信息
Trinity Preparatory School, Winter Park, FL, USA.
Department of Computer Science, University of Central Florida, Orlando, FL, USA.
出版信息
Sci Rep. 2022 Nov 8;12(1):18962. doi: 10.1038/s41598-022-23060-9.
Hypoxia inducible factor 1 alpha (HIF1A) is a transcription factor (TF) that forms highly structural and functional protein-protein interactions with other TFs to promote gene expression in hypoxic cancer cells. However, despite the importance of these TF-TF interactions, we still lack a comprehensive view of many of the TF cofactors involved and how they cooperate. In this study, we systematically studied HIF1A cofactors in eight cancer cell lines using the computational motif mining tool, SIOMICS, and discovered 201 potential HIF1A cofactors, which included 21 of the 29 known HIF1A cofactors in public databases. These 201 cofactors were statistically and biologically significant, with 19 of the top 37 cofactors in our study directly validated in the literature. The remaining 18 were novel cofactors. These discovered cofactors can be essential to HIF1A's regulatory functions and may lead to the discovery of new therapeutic targets in cancer treatment.
缺氧诱导因子 1 阿尔法（HIF1A）是一种转录因子（TF），它与其他 TF 形成高度结构和功能的蛋白-蛋白相互作用，以促进缺氧癌细胞中的基因表达。然而，尽管这些 TF-TF 相互作用非常重要，但我们仍然缺乏对许多涉及的 TF 共因子以及它们如何合作的全面了解。在这项研究中，我们使用计算基序挖掘工具 SIOMICS 系统地研究了八种癌细胞系中的 HIF1A 共因子，发现了 201 个潜在的 HIF1A 共因子，其中包括公共数据库中 29 个已知 HIF1A 共因子中的 21 个。这些 201 个共因子在统计学和生物学上都是有意义的，在我们的研究中排名前 37 的共因子中有 19 个在文献中直接得到验证。其余的 18 个是新的共因子。这些发现的共因子可能对 HIF1A 的调节功能至关重要，并可能导致癌症治疗中新的治疗靶点的发现。
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