Translational research : the journal of laboratory and clinical medicine
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Review
Role of epigenetic mechanisms in epithelial-to-mesenchymal transition of breast cancer cells.
The epithelial-to-mesenchymal transition (EMT) is a crucial process during normal development that allows dynamic and reversible shifts between epithelial and mesenchymal cell states. Cancer cells take advantage of the complex, interrelated cellular networks that regulate EMT to promote their migratory and invasive capabilities. ⋯ The authors review the current knowledge of alterations of epigenetic machinery, including DNA methylation, histone modifications, nucleosome remodeling and expression of microRNAs, associated with EMT and tumor progression of breast cancer cells. Last, existing and upcoming drug therapies targeting epigenetic regulators and their potential benefit for developing novel treatment strategies are discussed.
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Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Recent work by our and other groups has identified strong genetic predisposition factors for the development of pulmonary fibrosis, and cigarette smoke remains the most strongly associated environmental exposure risk factor. ⋯ Moreover, epigenetic marks represent a promising therapeutic target for IPF. In this review, the disease is introduced, genetic and gene expression studies in IPF are summarized, exposures relevant to IPF and known epigenetic changes associated with cigarette smoke exposure are discussed, and epigenetic studies conducted so far in IPF are summarized. Limitations, challenges, and future opportunities in this field are also discussed.
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Review
Epigenetic enzymes are the therapeutic targets for CD4(+)CD25(+/high)Foxp3(+) regulatory T cells.
CD4(+)CD25(+/high)Foxp3(+) regulatory T (Treg) cells are a subset of CD4(+) T cells that play an essential role in maintaining peripheral immune tolerance. Several transcriptional cofactors have been recently identified, which form complexes with transcription factor Foxp3 of Treg cells and contribute in the suppressive function of Treg cells. However, Foxp3 is still defined as a "master" (multiple pathway) regulator gene that controls the development and stability of Treg cells. ⋯ Recent progress suggests that the epigenetic mechanisms responsible for regulating the Foxp3 gene expression are key components of suppressive activity of Treg cells. This review not only discusses the basic concepts of biology and epigenetic modifications of Treg cells, but also analyzes the translational clinical aspect of epigenetic modifications of Treg cells, focusing on several ongoing clinical trials and the Food and Drugs administration (FDA) approved epigenetic-based drugs. The new progress in identifying epigenetic enzymes functional in Treg cells is a new target for the development of novel therapeutic approaches for autoimmune and inflammatory diseases, graft-vs-host disease and cancers.
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Alzheimer's disease (AD) is a large and growing public health problem. It is characterized by the accumulation of amyloid β peptides and abnormally phosphorylated tau proteins that are associated with cognitive decline and dementia. Much has been learned about the genomics of AD from linkage analyses and, more recently, genome-wide association studies. ⋯ We are in the midst of 2 large studies of human brains including coverage of more than 420,000 autosomal cytosine-guanine dinucleotides with the Illumina Infinium HumanMethylation450 BeadArray, and histone acetylation with chromatin immunoprecipitation sequencing. We present descriptive data to help inform other researchers what to expect from these approaches to better design and power their studies. We then discuss future directions to inform on the epigenomic architecture of AD.
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Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development or maintenance of persistent pain and possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain.