DataSheet_4_ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types.pdf

Anti-silencing function 1B histone chaperone (ASF1B) is known to be an important modulator of oncogenic processes, yet its role in lung adenocarcinoma (LUAD) remains to be defined. In this study, an integrated assessment of The Cancer Genome Atlas (TCGA) and genotype-tissue expression (GTEx) datasets revealed the overexpression of ASF1B in all analyzed cancer types other than LAML. Genetic, epigenetic, microsatellite instability (MSI), and tumor mutational burden (TMB) analysis showed that ASF1B was regulated by single or multiple factors. Kaplan-Meier survival curves suggested that elevated ASF1B expression was associated with better or worse survival in a cancer type-dependent manner. The CIBERSORT algorithm was used to evaluate immune microenvironment composition, and distinct correlations between ASF1B expression and immune cell infiltration were evident when comparing tumor and normal tissue samples. Gene set enrichment analysis (GSEA) indicated that ASF1B was associated with proliferation- and immunity-related pathways. Knocking down ASF1B impaired the proliferation, affected cell cycle distribution, and induced cell apoptosis in LUAD cell lines. In contrast, ASF1B overexpression had no impact on the malignant characteristics of LUAD cells. At the mechanistic level, ASF1B served as an indirect regulator of DNA Polymerase Epsilon 3, Accessory Subunit (POLE3), CDC28 protein kinase regulatory subunit 1(CKS1B), Dihydrofolate reductase (DHFR), as established through proteomic profiling and Immunoprecipitation-Mass Spectrometry (IP-MS) analyses. Overall, these data suggested that ASF1B serves as a tumor promoter and potential target for cancer therapy and provided us with clues to better understand the importance of ASF1B in many types of cancer.

抗沉默功能1B组蛋白伴侣（ASF1B）被誉为癌基因过程的调控者，然而其在肺腺癌（LUAD）中的作用尚待明确。本研究通过对癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据集的整合评估，揭示了ASF1B在除LAML以外的所有分析癌症类型中的高表达。遗传学、表观遗传学、微卫星不稳定性（MSI）和肿瘤突变负荷（TMB）分析显示，ASF1B的表达受单一或多个因素调控。Kaplan-Meier生存曲线表明，ASF1B表达升高与癌症类型相关的生存结果呈正相关或负相关。CIBERSORT算法用于评估免疫微环境组成，当比较肿瘤与正常组织样本时，ASF1B表达与免疫细胞浸润之间的显著相关性显而易见。基因集富集分析（GSEA）表明，ASF1B与增殖和免疫相关通路相关。敲低ASF1B损害了LUAD细胞系的增殖，影响了细胞周期分布，并诱导细胞凋亡。相反，ASF1B的过表达对LUAD细胞的恶性特征没有影响。在机制层面，通过蛋白质组学和免疫沉淀-质谱分析（IP-MS）证实，ASF1B作为DNA聚合酶Epsilon 3，辅助亚基（POLE3）、CDC28蛋白激酶调节亚基1（CKS1B）、二氢叶酸还原酶（DHFR）的间接调控因子。总体而言，这些数据表明ASF1B充当肿瘤促进因子，并成为癌症治疗的潜在靶点，为我们更好地理解ASF1B在多种癌症类型中的重要性提供了线索。