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epigenetic silence

Andriy Bilichak, Igor Kovalchuk
Virus-induced gene silencing (VIGS) is a powerful epigenetic tool that allows in a relatively short period of time to down-regulate the expression of an endogenous gene in infected plants for either monitoring the resulting phenotype or enhancing/modifying a particular trait associated with the gene. Here, we describe the utilization of Tobacco rattle virus (TRV) as a vector for the VIGS technique in Arabidopsis plants. The unique ability of TRV to infect both somatic tissues and gametes allows deciphering the role of genes in these tissues simultaneously...
2017: Methods in Molecular Biology
Haniyeh Eyvani, Farima Moghaddaskho, Majid Kabuli, Ali Zekri, Majid Momeny, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
AIMS: Cell cycle dysregulation is important in tumorigenesis. Transcriptional silencing of cell cycle regulatory genes, due to DNA methylation, is a common epigenetic event in malignancies. As2O3 has been shown to induce cell cycle arrest and also to be a potential hypomethylating agent. Our study aimed to investigate DNA methylation patterns of cell cycle regulatory genes promoters, the effects of Arsenic trioxide (As2O3) on the methylated genes and cell cycle distribution in colorectal cancer (CRC) cell lines...
October 18, 2016: Life Sciences
X Mu, S Ahmad, S Hur
The ability to distinguish between self and nonself is the fundamental basis of the immune system in all organisms. The conceptual distinction between self and nonself, however, breaks down when it comes to endogenous retroviruses and other retroelements. While some retroelements retain the virus-like features including the capacity to replicate and reinvade the host genome, most have become inactive through mutations or host epigenetic silencing. And yet, accumulating evidence suggests that endogenous retroelements, both active and inactive, play important roles not only in pathogenesis of immune disorders, but also in proper functioning of the immune system...
2016: Advances in Immunology
Katharina Meier, Stefan K Drexler, Franziska C Eberle, Karine Lefort, Amir S Yazdi
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC...
2016: PloS One
Nina Xie, He Gong, Joshua A Suhl, Pankaj Chopra, Tao Wang, Stephen T Warren
Fragile X syndrome (FXS) is a common cause of intellectual disability that is most often due to a CGG-repeat expansion mutation in the FMR1 gene that triggers epigenetic gene silencing. Epigenetic modifying drugs can only transiently and modestly induce FMR1 reactivation in the presence of the elongated CGG repeat. As a proof-of-principle, we excised the expanded CGG-repeat in both somatic cell hybrids containing the human fragile X chromosome and human FXS iPS cells using the CRISPR/Cas9 genome editing. We observed transcriptional reactivation in approximately 67% of the CRISPR cut hybrid colonies and in 20% of isolated human FXS iPSC colonies...
2016: PloS One
Qiang Fu, Huijun Shi, Chuangfu Chen
MicroRNAs (miRNAs) are an important class of small, non-coding RNAs that control target genes expression by degradation of target mRNAs or by inhibiting protein translation in many biological processes and cellular pathways. In a previous study, we found that miR-29b interfered with bovine viral diarrhea virus (BVDV) replication. However, the mechanisms of regulation of miR-29b expression are not well known. DNA methylation is an important epigenetic mechanism for silencing gene transcription, and plays an important role in promoter choice, protein expression, and regulation of miRNAs expression...
October 20, 2016: Archives of Virology
Yong Zhang, Bing Yu, Jun He, Daiwen Chen
Skeletal muscle is a remarkably complicated organ comprising many different cell types, and it plays an important role in lifelong metabolic health. Nutrients, as an external regulator, potently regulate skeletal muscle development through various internal regulatory factors, such as mammalian target of rapamycin (mTOR) and microRNAs (miRNAs). As a nutrient sensor, mTOR, integrates nutrient availability to regulate myogenesis and directly or indirectly influences microRNA expression. MiRNAs, a class of small non-coding RNAs mediating gene silencing, are implicated in myogenesis and muscle-related diseases...
2016: International Journal of Biological Sciences
Yan Long, Wen-Bin Tsai, Jeffrey T Chang, Marcos Estecio, Medhi Wangpaichitr, Naramol Savaraj, Lynn G Feun, Helen H W Chen, Macus Tien Kuo
Many human tumors require extracellular arginine (Arg) for growth because the key enzyme for de novo biosynthesis of Arg, argininosuccinate synthetase 1 (ASS1), is silenced. These tumors are sensitive to Arg-starvation therapy using pegylated arginine deiminase (ADI-PEG20) which digests extracellular Arg. Many previous studies reported that ASS1 silencing is due to epigenetic inactivation of ASS1 expression by DNA methylation, and that the demethylation agent 5-aza-deoxycytidine (Aza-dC) can induce ASS1 expression...
September 28, 2016: Oncotarget
J Z Zhao, X Q Zheng, M Gao
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid and protein phosphatase that functions as a tumor suppressor. PTEN regulates the multiple biological processes such as cell proliferation, invasion, metastasis, apoptosis and stem cell self-renewal through the phosphatidylinositol 3-kinase/ protein kinase B signaling pathway. PTEN activity can be modulated by mutations, epigenetic silencing, transcriptional repression, post-transcriptional contral and post-translational modifications.
October 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Francesca Megiorni, Simona Camero, Simona Ceccarelli, Heather P McDowell, Olga Mannarino, Francesco Marampon, Barry Pizer, Rajeev Shukla, Antonio Pizzuti, Cinzia Marchese, Anna Clerico, Carlo Dominici
Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27...
October 15, 2016: Oncotarget
Yu-Chuan Huang, Chung-Ta Lee, Jenq-Chang Lee, Yao-Wen Liu, Ying-Jen Chen, Joseph T Tseng, Jui-Wen Kang, Bor-Shyang Sheu, Bo-Wen Lin, Liang-Yi Hung
MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis...
October 18, 2016: Oncotarget
Wei-Min Chang, Yuan-Feng Lin, Chia-Yi Su, Hsuan-Yu Peng, Yu-Chan Chang, Tsung-Ching Lai, Guan-Hsun Wu, Yuan-Ming Hsu, Li-Hsing Chi, Jenn-Ren Hsiao, Chi-Long Chen, Jang-Yang Chang, Yi-Shing Shieh, Michael Hsiao, Shine-Gwo Shiah
Epigenetic correlates of head and neck cancer may illuminate its pathogenic roots. Through a gene set enrichment analysis, we found that the oncogenic transcription factor RUNX2 is widely upregulated in head and neck squamous cell carcinoma (HNSCC) with lymph node metastasis, where it also predicts poor prognosis in HNSCC patients. Enforced expression of ectopic RUNX2 promoted the metastatic capabilities of HNSCC, whereas RUNX2 silencing inhibited these features. Mechanistic investigations showed that manipulating levels of activin A (INHBA) could rescue or compromise the RUNX2-mediated metastatic capabilities of HNSCC cells...
October 19, 2016: Cancer Research
Chenran Zhang, Wei Meng, Jiajia Wang, Yicheng Lu, Guohan Hu, Liuhua Hu, Jie Ma
Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1), a strong tumor suppressor, is silenced in many human cancers. Our previous studies showed that RIZ1 expression was negatively correlated with the grade of glioma and was a key predictor of patient survival. Therefore, RIZ1 could be a potential tumor suppressor during glioma pathogenesis, although the mechanism underlying RIZ1 gene inactivation in gliomas is unknown. We investigated the methylation status of the RIZ1 promoter in human glioma tissues and four glioblastoma (GBM) cell lines, and verified the effect of the methyltransferase inhibitor 5-aza-2-deoxycytidine (5-aza-CdR) on RIZ1 transcription and cell proliferation...
October 18, 2016: Cellular and Molecular Neurobiology
Hubo Li, Brenton G Mar, Huadi Zhang, Rishi V Puram, Francisca Vazquez, Barbara A Weir, William C Hahn, Benjamin Ebert, David Pellman
Acute myeloid leukemia (AML) is a heterogeneous disease with complex molecular pathophysiology. To systematically characterize AML's genetic dependencies, we conducted genome-scale shRNA screens in 17 AML cell lines and analyzed dependencies relative to parallel screens in 199 cell lines of other cancer types. We identified 353 genes specifically required for AML cell proliferation. To validate the in vivo relevance of genetic dependencies observed in human cell lines, we performed a secondary screen in a syngeneic murine AML model driven by the MLL-AF9 oncogenic fusion protein...
October 18, 2016: Blood
Mariko Kikuchi, Hiroshi Katoh, Mina Waraya, Yoko Tanaka, Satoru Ishii, Toshimichi Tanaka, Nobuyuki Nishizawa, Keigo Yokoi, Naoko Minatani, Akira Ema, Yoshimasa Kosaka, Hirokazu Tanino, Keishi Yamashita, Masahiko Watanabe
Epigenetic silencing of HOPX has been shown frequent and specific in human cancers. HOPX is thought as a tumor suppressor gene and its promoter methylation is the main mechanism of down-regulation. In non-hereditary breast cancer, since roles of epigenetic modifications are more critical than in other cancers, the aim of this study is to seek into the roles and clinical relevance of epigenetic silencing of HOPX. Down-regulation of HOPX was observed in all human breast cancer cell lines tested. The promoter methylation was found in six of seven cell lines, and demethylating agents restored HOPX expression...
October 15, 2016: Cancer Letters
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
Jiajin Yang, Heng Ge, Caroline J Poulton, Susan L Hogan, Yichun Hu, Britta E Jones, Candace D Henderson, Elizabeth A McInnis, William F Pendergraft, J Charles Jennette, Ronald J Falk, Dominic J Ciavatta
BACKGROUND: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by destructive vascular inflammation. Two prominent ANCA autoantigens are myeloperoxidase (MPO) and proteinase 3 (PR3), and transcription of MPO and PRTN3, the genes encoding the autoantigens, is associated with disease activity. We investigated whether patients with AAV have alterations in histone modifications, particularly those associated with transcriptional activation, at MPO and PRTN3...
2016: Clinical Epigenetics
Dinesh Singh Tekcham, Satish S Poojary, Shushruta Bhunia, Mustafa Ahmed Barbhuiya, Sanjeev Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
BACKGROUND & OBJECTIVES: Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD. METHODS: Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues...
May 2016: Indian Journal of Medical Research
David Agustriawan, Chien-Hung Huang, Jim Jinn-Chyuan Sheu, Shan-Chih Lee, Jeffrey J P Tsai, Nilubon Kurubanjerdjit, Ka-Lok Ng
Epigenetic regulation has been linked to the initiation and progression of cancer. Aberrant expression of microRNAs (miRNAs) is one such mechanism that can activate or silence oncogenes (OCGs) and tumor suppressor genes (TSGs) in cells. A growing number of studies suggest that miRNA expression can be regulated by methylation modification, thus triggering cancer development. However, there is no comprehensive in silico study concerning miRNA regulation by direct DNA methylation in cancer. Ovarian serous cystadenocarcinoma (OSC) was therefore chosen as a tumor model for the present work...
October 1, 2016: Computational Biology and Chemistry
E Balada, L Felip, J Ordi-Ros, M Vilardell-Tarrés
We evaluated the transcriptional expression of DUSP23 in CD4+ T cells from 30 SLE patients and 30 healthy controls. DUSP23 mRNA levels were considerably higher in the patients group: 1,490 ± 1,713 versus 294,1 ± 204,2. None association was found between DUSP23 mRNA expression and the presence of typical serological and clinical parameters associated to SLE. Meaningful statistical values were obtained in the patients group between the levels of DUSP23 and ITGAL, PRF1, and CD40L. Similarly, transcript levels of different DNA methylation-related enzymes (DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4) were also positively correlated to the expression of DUSP23...
October 13, 2016: Clinical and Experimental Immunology
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