Beschreibung:
Abstract Hepatocellular carcinoma (HCC) is one of the frequently diagnosed cancers worldwide and has emerged as the main cause of cancer-related death with a very poor prognosis, which is closely related to cancer stem cell (CSC), a subset of cells known to be a root of tumor recurrence, metastasis, and chemoresistance in HCC. However, the characteristics of CSCs in hepatocellular carcinoma (HCC) are still elusive. Our previous in vitro hepatocyte differentiation model revealed that the expression of anti-silencing function 1B histone chaperone (ASF1B) was remarkably upregulated in the stem cell-like stages. In HCC patients, ASF1B was highly expressed in cancer tissues compared with normal counterparts and was positively correlated with poor survival. Functional assays indicated that ASF1B could considerably promote the self-renewal, growth, and metastasis of HCC both in vitro and in vivo. Mechanistically, ASF1B could directly bind to histone H3 Variant H3.3 and enhance its incorporation into the promoter regions of certain stemness- and metastasis-associated genes including SOX9, KLF4, and TBX3, contributing to their augmented transcriptional and protein expression levels. H3.3 knock-down decreased the expression of these stemness and metastasis-associated genes, eliminating the stemness and oncogenic properties of ASF1B. Overall, our study revealed that ASF1B could facilitate HCC stemness and progression via H3.3-dependent transcriptional reprogramming. ASF1B might be a novel diagnostic and prognostic biomarker for HCC patients. Citation Format: Xiaona Fang, Beilei Liu, Shan Liu, Yu Zhang, Lanqi Gong, Qian Yan, Xinyuan Guan. ASF1B potentiates stem cell traits and tumor progression in hepatocellular carcinoma via histone H3.3-dependent transcriptional reprogramming [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6065.