Although the importance of histone methylation in epigenetics was first suggested more than 50 years ago, research into histone modifications conducted in the past decade has led to an exponential increase in our understanding of histone H3 modifications. In particular, the involvement of H3 histone 27 lysine trimethylation in the development of various cancer phenotypes has been demonstrated. Unlike mutations in the DNA sequence, such epigenetic changes are reversible, suggesting that inhibitors of H3 histone 27 amino acid methylation enzymes could be used as anti-cancer agents. Here, we outline the regulatory functions of H3 histone 27 lysine trimethylation carried out by different enzymes, in carcinogenesis. We describe the role of H3 histone 27 lysine trimethylation as an important epigenetic regulatory mechanism in the development of various cancers via effects on inflammation, DNA damage repair, cell proliferation, cell metastasis, regulatory cell death, ferroptosis, and angiogenesis. Finally, we focus specifically on H3 histone 27 lysine trimethylation regulators and their future development as anti-cancer drugs.
Mesenchymal stem cell (MSC) has elicited great hopes for regenerative medicine, however, its regenerative potential decreases with age, which raises questions about the efficiency of autologous transplantations in elderly patients. To elucidate the cellular consequences and epigenetic mechanisms of aging, the functional and epigenetic changes in bone marrow derived MSC (BMSC) from normal and aging rats were studied concurrently. The results demonstrate that the proliferation and differentiation abilities of BMSCs from aging rats declined compared with those from young rats. In order to identify which miRNA involve in the senescence of BMSC, miRNA expression profiles of both BMSCs from young and aging rats were examined. The results showed that miR-146a expression increased significantly in BMSCs from aging rats compared with that from young rats, following with a decrease in Calcium/calmodulin-dependent Serine protein kinase (CASK) expression. Inhibition of miR-146a can reduces the numbers of senescent cells and stimulates the differentiation of BMSC. Luciferase assay demonstrated that CASK was a direct target of miR-146a, inhibition of miR-146a significantly elevated the expression of CASK. Overexpression of CASK in aged BMSC can rescue its proliferation and differentiation abilities. All these results indicate that miR-146a may cause aging and senescence of BMSC through the inhibition of CASK expression, which may be potential target for BMSC aging and some age-related disease.
The increased accumulation of lactate in tumor microenvironment is a characteristic feature of tumorigenesis, which affects various biological processes such as metabolism and immune response. The specific role of lactate remains elusive in DNA damage response (DDR) and maintenance of genome stability. A recent study unveiled a novel modification—lactylation on MRE11, a key player of DDR, —stemming from cellular lactate metabolites within homologous recombination (HR) repair. This study links cancer metabolism to DNA double-strand break (DSB) repair, proposing a potential therapeutic strategy in future cancer treatment by targeting this process.