Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy.
Sci Rep. 2021 Dec 9;11(1):23764. doi: 10.1038/s41598-021-03027-y.
NF-Y is a pioneer transcription factor-TF-formed by the Histone-like NF-YB/NF-YC subunits and the regulatory NF-YA. It binds to the CCAAT box, an element enriched in promoters of genes overexpressed in many types of cancer. NF-YA is present in two major isoforms-NF-YAs and NF-YAl-due to alternative splicing, overexpressed in epithelial tumors. Here we analyzed NF-Y expression in stomach adenocarcinomas (STAD). We completed the partitioning of all TCGA tumor samples (450) according to molecular subtypes proposed by TCGA and ACRG, using the deep learning tool DeepCC. We analyzed differentially expressed genes-DEG-for enriched pathways and TFs binding sites in promoters. CCAAT is the predominant element only in the core group of genes upregulated in all subtypes, with cell-cycle gene signatures. NF-Y subunits are overexpressed, particularly NF-YA. NF-YAs is predominant in CIN, MSI and EBV TCGA subtypes, NF-YAl is higher in GS and in the ACRG EMT subtypes. Moreover, NF-YAl tumors correlate with a discrete Claudin cohort. Elevated NF-YB levels are protective in MSS;TP53 patients, whereas high NF-YAl/NF-YAs ratios correlate with worse prognosis. We conclude that NF-Y isoforms are associated to clinically relevant features of gastric cancer.
NF-Y 是一种先驱转录因子，由组蛋白样 NF-YB/NF-YC 亚基和调节性 NF-YA 组成。它结合 CCAAT 盒，CCAAT 盒是许多类型癌症中过度表达的基因启动子中富含的元件。NF-YA 由于选择性剪接，存在两种主要的同工型-NF-YAs 和 NF-YAl-在上皮肿瘤中过度表达。在这里，我们分析了胃腺癌（STAD）中的 NF-Y 表达。我们使用深度学习工具 DeepCC，根据 TCGA 和 ACRG 提出的分子亚型对所有 TCGA 肿瘤样本（450 个）进行了分区。我们分析了差异表达基因（DEG），以研究启动子中富集的途径和 TF 结合位点。CCAAT 仅在所有亚型上调的核心基因群中是主要元件，具有细胞周期基因特征。NF-Y 亚基过表达，特别是 NF-YA。NF-YAs 在 CIN、MSI 和 EBV TCGA 亚型中占优势，NF-YAl 在 GS 和 ACRG EMT 亚型中较高。此外，NF-YAl 肿瘤与离散的 Claudin 队列相关。在 MSS；TP53 患者中，升高的 NF-YB 水平具有保护作用，而高 NF-YAl/NF-YAs 比值与预后较差相关。我们得出结论，NF-Y 同工型与胃癌的临床相关特征相关。
