Roles and regulation of histone acetylation in hepatocellular carcinoma

Abstract

Hepatocellular Carcinoma (HCC) is the most frequent malignant tumor of the liver, but its prognosis is poor. Histone acetylation is an important epigenetic regulatory mode that modulates chromatin structure and transcriptional status to control gene expression in eukaryotic cells. Generally, histone acetylation and deacetylation processes are controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Dysregulation of histone modification is reported to drive aberrant transcriptional programmes that facilitate liver cancer onset and progression. Emerging studies have demonstrated that several HDAC inhibitors exert tumor-suppressive properties via activation of various cell death molecular pathways in HCC. However, the complexity involved in the epigenetic transcription modifications and non-epigenetic cellular signaling processes limit their potential clinical applications. This review brings an in-depth view of the oncogenic mechanisms reported to be related to aberrant HCC-associated histone acetylation, which might provide new insights into the effective therapeutic strategies to prevent and treat HCC.

Lactobacillus acidophilus suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma through producing valeric acid

“…In addition, dysregulated activation of HDAC, the major epigenetic mediator of histone modification, is known to be pro-tumourigenic and many studies have reported the use of HDAC inhibitors against HCC. 35 Here, we showed that valeric acid markedly constrains hepatic HDAC activity of NAFLD-HCC mice, consistent with a study reporting that valeric acid could act as HDAC inhibitor against hepatocarcinogenesis. 19 …”

The role of sex hormones and receptors in HBV infection and development of HBV‐related HCC

“…Histone deacetylases (HDACs) reduce the activity of the target gene by removing the acetylase from the lysine residue on the histone and restoring the positive charge of the lysine. 70 HBx protein is also closely related to HDACs activities, HBV induced higher activity of HDAC1 in HCC tissue than adjacent tissue in HBV-related HCC. 71 Studies found that HBx-suppress ESR1 transcriptional activity by HDAC1, and additional Trichostatin A administration could restore ESR1 transcriptional activity.…”

“…But whether HBx directly recruits DNMTs to the promoter of ESR1 is unclear. Histone deacetylases (HDACs) reduce the activity of the target gene by removing the acetylase from the lysine residue on the histone and restoring the positive charge of the lysine 70 . HBx protein is also closely related to HDACs activities, HBV induced higher activity of HDAC1 in HCC tissue than adjacent tissue in HBV‐related HCC 71 .…”

The acetyltransferase BmCBP can catalyze the acetylation modification of BmSP3 and affect its protein expression in silkworm, Bombyx mori

“…Acetylation modi cation was rstly found in histone proteins [21]. With the development of mass spectrometry technology, reversible acetylation modi cation was also found in non-histone proteins and is widely involved in many different cellular processes, such as transcriptional regulation [22][23][24][25], DNAprotein interaction [26,27], subcellular localization [28,29], cell processes [30], cell division and protein folding [31], and DNA damage repair [32,33]. In addition, non-histone acetylation modi cation can also affect protein function by regulating protein stability [34].…”