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Epigenetic dysregulation drives aberrant transcriptional programs playing a critical role in hepatocellular carcinoma (HCC), which may provide novel insights into the heterogeneity of HCC. This study performed an integrated exploration on the epigenetic dysregulation of miRNA and methylation. We discovered and validated three patterns endowed with gene-related transcriptional traits and clinical outcomes. Specially, a stemness/epithelial-mesenchymal transition (EMT) subtype was featured by immune exhaustion and the worst prognosis. Besides, MMP12, a characteristic gene, was highly expressed in the stemness/EMT subtype, which was verified as a pivotal regulator linked to the unfavorable prognosis and further proven to promote tumor proliferation, invasion, and metastasis in vitro experiments. Proteomic analysis by mass spectrometry sequencing also indicated that the overexpression of MMP12 was significantly associated with cell proliferation and adhesion. Taken together, this study unveils innovative insights into epigenetic dysregulation and identifies a stemness/EMT subtype-specific gene, MMP12, correlated with the progression and prognosis of HCC.
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http://dx.doi.org/10.1021/acs.jproteome.4c00036 | DOI Listing |
Front Pharmacol
August 2025
Stem Cell Research Center, Department of Pathology and Pathophysiology, School of Medicine, Tongji University, Shanghai, China.
Bladder cancer (BC) is a disease that predominantly affects older adults, with aging playing a critical role in its onset and progression. Age-associated phenomena, including immunosenescence and chronic inflammation, form a pro-tumor milieu, while genomic instability and epigenetic drift further increase cancer risk. The review highlights the dual role of DNA methylation in BC: global hypomethylation can activate transposable elements and oncogenes, whereas focal hypermethylation silences tumor-suppressor genes like CDKN2A, especially detrimental in older tissues that rely on these genes for senescence control.
View Article and Find Full Text PDFFront Cell Dev Biol
August 2025
Laboratory of Rheumatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Introduction: Nephropathic cystinosis is a rare genetic disorder characterized by cystine accumulation in lysosomes that causes early renal dysfunction and progressive chronic kidney disease. Although several metabolic pathways, including oxidative stress and inflammation, have been implicated in the progression of renal parenchyma damage, the precise mechanisms driving its progression are not fully understood. Recent studies suggest that epigenetic modifications, particularly DNA methylation (DNAm), play a critical role in the development of chronic kidney disease.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
August 2025
School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia.
Transcription factors are significant regulators of gene expression in most biological processes related to diabetes, including beta cell (β-cell) development, insulin secretion and glucose metabolism. Dysregulation of transcription factor expression or abundance has been closely associated with the pathogenesis of type 1 and type 2 diabetes, including pancreatic and duodenal homeobox 1 (), neurogenic differentiation 1 (), and forkhead box protein O1 (). Gene expression is regulated at the transcriptional level by transcription factor binding, epigenetically by DNA methylation and chromatin remodelling, and post-transcriptional mechanisms, including alternative splicing and microRNA (miRNA).
View Article and Find Full Text PDFCurr Opin Rheumatol
September 2025
University Medical Centre Ljubljana, Department of Rheumatology, Ljubljana.
Purpose Of Review: This review examines how metabolic reprogramming drives fibrosis and immune dysregulation in systemic sclerosis (SSc), emphasizing the role of nutrient-sensing and energy pathways in disease progression.
Recent Findings: SSc is characterized by a shift from catabolic to anabolic metabolism, defined by reduced AMP-activated protein kinase (AMPK) and enhanced mechanistic target of rapamycin complex 1 (mTORC1) signaling. This promotes biosynthetic activity, with upregulated glycolysis supplying substrates for collagen production and supporting pro-inflammatory immune cell polarization.
J Genet Genomics
September 2025
Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Sh
Chromodomain helicase DNA binding protein 7 (CHD7), an ATP-dependent chromatin remodeler, plays versatile roles in neurodevelopment. However, the functional significance of its ATPase/nucleosome remodeling activity remains incompletely understood. Here, we generate genetically engineered mouse embryonic stem cell lines harboring either an inducible Chd7 knockout or an ATPase-deficient missense variant identified in individuals with CHD7-related disorders.
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