Journal of clinical epigenetics最新文献

Introduction: Type 2 Diabetes (T2D) is a common chronic disease with substantial disease burden and economic impact. Lifestyle changes can significantly alter the course of the disease, if detected at an early stage. DNA methylation signature may serve as a biomarker for early detection of increased T2D risk.

Design: DNA methylation profiling was performed using the Illumina Infinium Human Methylation 450K Bead chip array in 24 normoglycemic Old Order Amish (OOA) individuals who later developed Impaired Fasting Glucose (IFG) (cases), and 24 OOA individuals who remained normoglycemic after an average follow up of 10 years (controls). Cases and controls were matched on age, sex, BMI, baseline fasting glucose, and glucose level after 2 h from 75 g Oral Glucose Tolerance Test (OGTT).

Results: Association analysis found no significant difference in either global methylation or individual probe methylation between cases and controls, however, the top 34 suggestive significant sites were located in genes with interesting biological links to T2D and glycemic traits. These genes include BTC that plays a role in pancreatic cell proliferation and insulin secretion, ITGA1 a known bone mineral density gene that was recently found to be associated also with T2D and glycemic traits, and may explain the link between T2D and BMD, and RPTOR and TSC2 both of which are part of insulin signaling pathway.

Conclusions: These results may shed light on the initiation and development of hyperglycemia and T2D and help to identify high risk individuals for early intervention; however, further studies are required for validation.

Cells release into the extracellular environment, diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles. A number of studies indicate that these extracellular vehicles (EVs) mediate the interaction between cancer cells and their microenvironment; and thereby, play a critical role in the development of cancers. EVs contain cargo which consist of proteins, lipids, mRNAs, and miRNAs that can be delivered to different types of cells in nascent as well as distal locations. Discovery of this latter cargo has drawn an increasing amount of attention, due to their altering effects on the transcriptome, proteins, and subsequent cellular characteristics in recipient cells. Cancer cell derived exosomes (CCEs) have been identified in body fluids of cancer patients including urine, plasma and saliva. Because CCE content largely depends on tumor type and stage, they invariably lend great potential in serving as prognostic and diagnostic markers. Notably, accumulating evidence demonstrates that EV-derived miRNAs have key roles in regulating various aspects of cellular homeostasis, including proliferation, survival, migration, metastasis, and the immune system etc. More recently, diagnostic and therapeutic exploitation of stem cells derived EVs are under investigation. This review aims to summarize recent advances in EV-derived miRNAs in a variety of tumor types, and suggests that these cancer-derived exosomal miRNAs play a critical role in regulating cellular functions in surrounding and distant locations. It also discusses the role of adverse environmental exposure in altering stem cell exosomal miRNA profiling, which we believe leads to changes in the extracellular environment as well as a diverse range of biological processes.