H2A.Z acetylation by lincZNF337-AS1 via KAT5 implicated in the transcriptional misregulation in cancer signaling pathway in hepatocellular carcinoma

Abstract

In eukaryotes, histones and their variants are essential for chromatin structure and function; both play important roles in the regulation of gene transcription, as well as the development of tumors. We aimed to explore the genomics data of hepatocellular carcinoma (HCC), combined with literature analysis, in terms of the histone variant H2A.Z. Cell phenotype assay confirmed the effect of H2A.Z on the proliferation, metastasis, apoptosis, and cell cycle of HCC cells. H2A.Z was shown to function via the tumor dysregulation signaling pathway, with BCL6 as its interacting protein. In addition, the acetylation level of H2A.Z was higher in HCC and was related to tumor formation. We found the acetylation of H2A.Z to be related to and regulated by lincZNF337-AS1. LincZNF337-AS1 was found to bind to H2A.Z and KAT5 at different sites, promoting the acetylation of H2A.Z through KAT5. We concluded that, in HCC, H2A.Z is an oncogene, whose acetylation promotes the transcription of downstream genes, and is regulated by lincZNF331-AS1.

Roles and regulation of histone acetylation in hepatocellular carcinoma

“…The cellular levels and biological activities of these enzymes provide a direct link between epigenetic modifications and the control of cancer signaling, transcription, and cell growth. Furthermore, acetylation of histone variant H2A.Z is also implicated in the transcriptional misregulation in cancer signaling pathway in HCC ( Yuan et al, 2021 ). Aberrant regulation by acetylation on these signaling pathways and biological processes resulted in carcinogenesis and progression of HCC.…”

Abrine Elicits Liver Carcinoma Immunity and Enhances Antitumor Efficacy of Immune Checkpoint Blockade by Modulating PD-L1 Signaling

“…Increasing studies in some preclinical models have indicated that epigenetic modulators participate in the regulation of immune response, suggesting that targeting epigenetic process is a rationale strategy for cancer therapy [ 29 – 31 ]. Recent studies have found that z-acetylation of KAT5 is associated with transcriptional misregulation of tumor signaling pathways in hepatocellular carcinoma, suggesting that KAT5 may be involved in the pathogenesis of hepatocellular carcinoma [ 32 ]. We discovered decreased level of KAT5 in liver cancer cells after abrine treatment.…”

Genomic analyses identify key molecules and significant signaling pathways in Sorafenib treated hepatocellular cancer cells

“…Similarly, Hyuk Moon found that MAPK is frequently activated in liver cancer, which follows by a number of genetic mutations in Hepatocellular cancer cells 26 . The study by Yin Yuan et al found that lincZNF337 can acetylate the H2A via KAT5 to further transcriptionally misregulate the cancer signaling pathway in liver cancer 27 .…”