P-152 Involvement of FOXM1-regulated histone chaperone ASF1B in gastric cancer growth

Histone chaperone is important for nucleosome assembly during DNA replication. Interestingly, recent efforts have shed light on the role of histone chaperones in aggressive progression of multiple cancers. Though ASF1B plays a critical role in DNA replication and in cancer progression. Nevertheless, the underlying mechanism and the regulatory network of ASF1B in gastric cancer remain largely unknown. Bioinformatics approach was used to identify ASF1B interaction network in gastric cancer. The expression of ASF1B and its relationship with clinicopathological characteristics were tested by immunohistochemical staining. Cell viability was investigated by clone formation assay, cell counting kit-8, EdU proliferation assay in gastric cancer cells with or without ASF1B knockdown and overexpression. RNA-seq was performed to detect differential gene and gene enrichment of differential gene after knockdown of ASF1B. Flow cytometry and western blot were conducted to detect the effect of ASF1B on the cell cycle. The transcriptional regulation of ASF1B by transcription factor FOXM1 was detected via dual-luciferase reporter assay. Chromatin immunoprecipitation assay was employed to exam FOXM1 enrichment at ASF1B loci. Xenograft model was carried out to investigate the growth and progression of gastric cancer in mice. The high expression of ASF1B was associated with poor differentiation and unfavorable prognosis in gastric cancer. ASF1B knockdown hindered the malignant biological behavior of gastric cancer cells in vitro and in vivo, whereas ASF1B overexpression led to the opposite effect. FOXM1 regulated the transcription of ASF1B, and its mRNA levels in clinical tissues were highly correlated. Knockdown of ASF1B transcriptionally repressed PRDX3 expression, disrupting the balance of oxidative stress in gastric cancer cells. Our findings indicate the promotive role of ASF1B on gastric cancer progression and suggest ASF1B may serve as a novel potential therapeutic target for gastric cancer.