Current Pharmaceutical Design - Volume 20, Issue 11, 2014

Syncytin-1 plays a critical role in the maintenance of normal pregnancy by mediating the formation of syncytiotrophoblasts through a fosugenic action. Encoded by the human endogenous retrovirus envelope gene HERV-W, syncytin-1 trophoblast-specific expression is controlled by epigenetic mechanisms. In non-placental tissues, the syncytin-1 gene is suppressed by hypermethylation in the LTR promoter region. Hypomethylat Read More

Syncytin-1 is a protein coded by a human endogenous retrovirus (HERV) gene of the HERV-W family (HERVWE1). Syncytin- 1 mediates formation of syncytiotrophoblasts through fusion of cytotrophoblasts, a hallmark of terminal differentiation of placental trophoblast linage. Syncytin-1 also possesses nonfusogenic functions and regulates cell cycle progression. While decreased syncytin-1 expression and syncytium deficiency Read More

Background: Current therapeutic strategies for advanced prostate cancer (PCa) are largely ineffective. Because aberrant DNA methylation associated with inappropriate gene-silencing is a common feature of PCa, DNA methylation inhibitors might constitute an alternative therapy. In this study we aimed to evaluate the anti-cancer properties of RG108, a novel non-nucleoside inhibitor of DNA methyltransferases (DNMT), in Read More

DNA methylation plays an important role in epigenetics signaling, having an impact on gene regulation, chromatin structure and development. Within the family of de novo DNA methyltransferases two active enzymes, DNMT3A and DNMT3B, are responsible for the establishment of the proper cytosine methylation profile during development. Defects in DNMT3s function correlate with pathogenesis and progression of mo Read More

Epigenetic modulation captures the lack of correlation between the genotype and the phenotype. It also provides an interface between environment and the genotype leading to functional plasticity of the genome. While drug response can be modulated by the epigenome, the therapeutic intervention by drugs can also be considered as an environmental cue for epigenetic alterations. The effect of genetic poly Read More

The neuroepigenome, i.e., the epigenome of the nervous system, has become interesting for therapeutics in the last years due to widespread availability of dedicated drugs. A pivotal role for neuroepigenetics is certainly implied, both in physiology and pathology, by the highly dynamic structural and functional rearrangements that constantly occur into the nervous system, globally known as plasticity. Moreover, the idea Read More

Cognitive disorders are an important group of disorders affecting the brain for which currently used drugs are often of low efficacy and mainly of symptomatic value. There is increasing evidence suggesting that epigenetic changes in gene expression underlie cognitive disorders. Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs, that reverse epigenetic changes in gene expression. At present m Read More

Accumulating evidence suggested that epigenetic changes such as promoter-specific DNA hypermethylation and histone deacetylation cause tumor suppressor gene silencing and contribute to malignant transformation. Treatment of cancer cells with HDAC inhibitors can reactivate the expression of silenced genes, block the cell cycle, and induce cell apoptosis. In vitro experiments in cancer cell cultures and in vivo studies using mo Read More

Epigenetic changes including DNA methylation, histone modifications, chromatin remodeling and microRNAs play critical roles in tumorigenesis and tumor development. Reversal of epigenetic changes sensitizes some tumor cells to radiation. DNMT-I enhances the response of tumor cells to radiotherapy. AZA demethylated promoters of genes related to ionizing radiation response, such as p16 and hMLH1. The genes expressi Read More

Extensive evidence suggests that dysregulation of histone lysine acetylation is intimately linked with the development of cancer in epigenetic level. Histone acetylation on lysine is regulated mainly by the "pencil" ---Histone acetyltransferases (HATs) and the "eraser" –Histone deacetylases HDACs. Dramatic elevation of global histone deacetylation is considered as a biomarker for cancer. Therefore, current antitumor drug design oft Read More

Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated tumor. Response to progestin-based therapy correlates positively with progesterone receptor (PR) expression. However, many endometrial tumors have low levels or loss of PR, limiting the clinical application of progestin. We evaluated the ability of epigenetic modulators to restore functional PR expression in Type I endometrial can Read More

DNA methyltransferase (DNMT) and histone deacetylase are key enzymes mediating the epigenetic regulation of gene expression. DNA hypermethylation and/or histone deacetylation in promoter regions is often associated with downregulation or silencing of transcription. Epigenetic silencing of tumor suppressor genes plays an important role in malignant transformation. DNMT and HDAC inhibitors induce DNA demet Read More

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecologic malignancies. Despite great efforts to improve early detection and optimize chemotherapeutic regimens, the 5-year survival rate is only 30% for patients presenting with late-stage ovarian cancer. The high mortality of this disease is due to late diagnosis in over 70% of ovarian cancer cases. A class of small noncoding RNAs, or microRNAs, was found t Read More

Recently, a group of microRNAs (miRNAs), the miR-200 family (miR-200s) has been found to be deregulated in multiple types of cancers, in which this family of miRNAs was demonstrated to play a pivotal role in tumor initiation, maintenance, malignant metastasis and chemotherapy resistance. By targeting several central inducers of the epithelial-to-mesenchymal transition (EMT), e.g. ZEB1, ZEB2 and SLUG, miR-200s are curren Read More

G-protein coupled receptor 4 (GPR4) is a G protein-coupled receptor (GPCR) activated by sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC). Later studies indicated that GPR4 can serve as a proton sensor. GPR4 has been known to play a critical role in the tube formation of vascular endothelial cells, and GPR4 overexpression is observed in various types of malignancies, suggesting its involv Read More

Reactive oxygen species (ROS) plays a key role in carcinogenesis by aberrantly inducing signaling networks that initiatiate tumorigenesis and stimulate tumor progression. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate approximately 30% of the genes in a cell via degradation or translational inhibition of their target mRNAs. However, the effects of ROS o Read More