Metabolism-Associated Epigenetic and Immunoepigenetic Reprogramming in Liver Cancer

Abstract

Metabolic reprogramming and epigenetic changes have been characterized as hallmarks of liver cancer. Independently of etiology, oncogenic pathways as well as the availability of different energetic substrates critically influence cellular metabolism, and the resulting perturbations often cause aberrant epigenetic alterations, not only in cancer cells but also in the hepatic tumor microenvironment. Metabolic intermediates serve as crucial substrates for various epigenetic modulations, from post-translational modification of histones to DNA methylation. In turn, epigenetic changes can alter the expression of metabolic genes supporting on the one hand, the increased energetic demand of cancer cells and, on the other hand, influence the activity of tumor-associated immune cell populations. In this review, we will illustrate the most recent findings about metabolic reprogramming in liver cancer. We will focus on the metabolic changes characterizing the tumor microenvironment and on how these alterations impact on epigenetic mechanisms involved in the malignant progression. Furthermore, we will report our current knowledge about the influence of cancer-specific metabolites on epigenetic reprogramming of immune cells and we will highlight how this favors a tumor-permissive immune environment. Finally, we will review the current strategies to target metabolic and epigenetic pathways and their therapeutic potential in liver cancer, alone or in combinatorial approaches.

Biofluids Metabolic Profiling Based on PS@Fe3O4–NH2 Magnetic Beads-Assisted LDI-MS for Liver Cancer Screening

“…To fulfill the growth and appreciation of cancer tissue, more energetic needs and components are required. The Warburg shift is proposed in liver cancer progress; the glycolysis and TCA cycle lead to efficient and fast energy production . Except for glucose, other carbon sources also converse into precursors for other biomolecules, including some amino acids and lipids.…”

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice

“…Trained immune cells have many similar metabolic characteristics to cancer cells, for example, they are both energy-intensive cells, and have metabolic disorders, including amino acid and glucose metabolism disorders ( 56 – 58 ). The disorder of proline biosynthesis promotes the occurrence of various cancers, and proline is the “limiting amino acid” of cancer cells ( 29 , 59 ). In this study, the level of proline in the trained macrophages induced by PVM-OVA was significantly increased, compared with that in naïve macrophages.…”

Establishment of a novel glycolysis-immune-related diagnosis gene signature for endometriosis by machine learning

“…Whilst EM has benign clinical and pathological symptoms, it has cancer-like features such as spread, invasion, and hyperplasia [ 19 ]. Cancers with a significant Warburg effect develop a tumour microenvironment (TME) deprived of glucose, limiting local immune surveillance via nutritional competition [ 20 ]. Meanwhile, immune cells can promote glycolysis in the same way that tumour cells can.…”