ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types

Abstract

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.

Identification of Survival-Associated Hub Genes in Pancreatic Adenocarcinoma Based on WGCNA

“…As one of histone H3-H4 chaperone anti-silencing function 1 (ASF1) isoforms, ASF1B plays important roles in chromatin-based progression of cellular DNA replication and transcription regulation, especially in cell proliferation ( Paul et al, 2016 ). Accumulating evidence has shown that up-regulation of ASF1B stimulated cancer cell proliferation, DNA replication and migration, accompanied by restrained cell cycle arrest and apoptosis ( Misiewicz-Krzeminska et al, 2013 ; Han et al, 2018 ; Zhou et al, 2019 ; Liu X. et al, 2020 ; Zhang et al, 2021 ), which was also consistent with our enrichment analysis of module genes ( Figure 2A ). In addition, several studies have underlined the important prognostic impact of ASF1B on a variety of cancers ( Corpet et al, 2011 ; Chen Z. et al, 2021 ; Feng et al, 2021 ).…”

ASF1B Serves as a Potential Therapeutic Target by Influencing Cell Cycle and Proliferation in Hepatocellular Carcinoma

“…In this research, we used bioinformatics and multiple databases to comprehensively analyze the expression of ASF1B in pan-cancer, and found that ASF1B was abnormally expressed in most cancers, including liver cancer, which is consistent with current literature reports ( 27 – 29 ). In order to explore the relationship between ASF1B and HCC in detail, RNA-seq data and corresponding clinical data of HCC in TCGA were analyzed separately.…”

Identification of Tumor Mutation Burden, Microsatellite Instability, and Somatic Copy Number Alteration Derived Nine Gene Signatures to Predict Clinical Outcomes in STAD

“…More importantly, the expression levels of ASF1B were reported to be associated with TME in STAD ( Rossetti and Sacchi, 2020 ). From a mechanistic point of view, ASF1B indirectly regulated CKS1B to mediate growth, apoptosis, and cell cycle progression in cancers ( Zhang et al, 2021b ).…”