Histone modification: Biomarkers and potential therapies in colorectal cancer

Abstract

The complex mechanism of colorectal cancer development is closely associated with epigenetic modifications and is caused by overexpression and/or inactivation of oncogenes. Histone modifying enzymes catalyze histone modifications to alter gene expression, which plays a crucial role in the development and progression of colorectal cancer. Currently, there is more frequent study on histone acetylation, methylation, and phosphorylation, and their mechanisms in colorectal cancer development are clearer. This article elaborates on the role of histone modification in epigenetics in colorectal cancer development and discusses recent advances in using it as biomarkers and therapeutic targets for the treatment of colorectal cancer. The review aims to demonstrate the significant role of histone modification as a new therapeutic target in colorectal cancer and provides insights into the novel diagnostic and therapeutic options it offers.

Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases.

“…Histones are key epigenetic regulators. Their post-translational modifications (acetylation, methylation and phosphorylation) can be linked with gene expression changes that lead to cancer progression including CRC and hence are being investigated for their therapeutic and prognostic potential [ 32 ]. Histone H4 upregulation has been linked to platinum-based chemotherapy resistance in malignancies [ 33 ] and may explain its association with poor prognosis in our patient cohort.…”

Research progress and applications of epigenetic biomarkers in cancer

“…Methylation can occur at various sites, including H3 lysine (H3K) sites 4, 9, 27, 36, 79, and 20 of H4 lysine (H4K) (Hyun et al, 2017). According to several studies, specific methylation patterns, such as H3K9me3, H3K27me3, H3K36me3, and H4K20me3, serve as vital indicators for gastric, liver, breast, pancreatic, ovarian, and colon cancers (Sasidharan Nair et al, 2018;Sogutlu et al, 2022;An et al, 2023;Burlibasa et al, 2023;Tachaveeraphong and Phattarataratip, 2024). Furthermore, the expression of H3K9me2, H3K9me3, and H3K27me3 is Frontiers in Pharmacology frontiersin.org significantly associated with clinical pathologies and may serve as independent risk factors for survival assessment in patients with gastric cancer (Li et al, 2019).…”

Pharmacological inhibition of p300 ameliorates steatosis, inflammation, and fibrosis in mice with non-alcoholic steatohepatitis

“…These epigenetic modifications encompass histone modifications, DNA methylation, and non-coding RNAs. Posttranslational modifications of histones, such as acetylation, methylation, and phosphorylation of histone tails, regulate chromatin structure and gene expression [ 7 ]. Among them, acetylation is one of the most extensively studied.…”

“…Among them, acetylation is one of the most extensively studied. Histone acetylation is controlled by the opposing functions of histone acetyltransferases and histone deacetylases [ 7 ]. Within the family of histone acetyltransferases, p300 plays a pivotal role in multiple cellular processes, including apoptosis, proliferation, and differentiation, by regulating histone acetylation-dependent chromatin compactness and accessibility [ 8 ].…”