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RNA epigenetic

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https://www.readbyqxmd.com/read/28322996/assessing-the-mirna-sponge-potential-of-runx1t1-in-t-8-21-acute-myeloid-leukemia
#1
Alexander Junge, Roza Zandi, Jakob Hull Havgaard, Jan Gorodkin, Jack Bernard Cowland
t(8;21) acute myeloid leukemia (AML) is characterized by a translocation between chromosomes 8 and 21 and formation of a distinctive RUNX1-RUNX1T1 fusion transcript. This translocation places RUNX1T1 under control of the RUNX1 promoter leading to a pronounced upregulation of RUNX1T1 transcripts in t(8;21) AML, compared to normal hematopoietic cells. We investigated the role of highly-upregulated RUNX1T1 under the hypothesis that it acts as competing endogenous RNA (ceRNA) titrating microRNAs (miRNAs) away from their target transcripts and thus contributes to AML formation...
March 16, 2017: Gene
https://www.readbyqxmd.com/read/28320962/genetic-disruption-of-oncogenic-kras-sensitizes-lung-cancer-cells-to-fas-receptor-mediated-apoptosis
#2
Haiwei Mou, Jill Moore, Sunil K Malonia, Yingxiang Li, Deniz M Ozata, Soren Hough, Chun-Qing Song, Jordan L Smith, Andrew Fischer, Zhiping Weng, Michael R Green, Wen Xue
Genetic lesions that activate KRAS account for ∼30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras Here, we show that tumor cells can survive knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320778/the-epitranscriptome-of-noncoding-rnas-in-cancer
#3
REVIEW
Manel Esteller, Pier Paolo Pandolfi
The activity of RNA is controlled by different types of post-transcriptional modifications, such as the addition of methyl groups and other chemical and structural changes, that have been recently described in human cells by high-throughput sequencing. Herein, we will discuss how the so-called epitranscriptome is disrupted in cancer and what the contribution of its writers, readers, and erasers to the process of cellular transformation is, particularly focusing on the epigenetic modifications of ncRNAs.Significance: Chemical modifications of RNA play a central role in the control of messenger and ncRNA activity and, thus, are tightly regulated in cells...
March 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28319609/developmental-alterations-in-huntington-s-disease-neural-cells-and-pharmacological-rescue-in-cells-and-mice
#4
(no author information available yet)
Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#5
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315486/crispr-cas9-mediated-genome-editing-in-plants
#6
Xuejun Liu, Chuanxiao Xie, Huaijun Si, Jinxiao Yang
The increasing burden of the world's population on agriculture necessitates the development of more robust crops. As the amount of information from sequenced crop genomes increases, technology can be used to investigate the function of genes in detail and to design improved crops at the molecular level. Recently, an RNA-programmed genome-editing system composed of a clustered regularly interspaced short palindromic repeats (CRISPR)-encoded guide RNA and the nuclease Cas9 has provided a powerful platform to achieve these goals...
March 14, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28314754/kdm6b-regulates-cartilage-development-and-homeostasis-through-anabolic-metabolism
#7
Jun Dai, Dongsheng Yu, Yafei Wang, Yishan Chen, Heng Sun, Xiaolei Zhang, Shouan Zhu, Zongyou Pan, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang
OBJECTIVES: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms. METHODS: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic Col2a1-CreER(T2);Kdm6b(f/f) ...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28306719/chromosome-19q13-disruption-alters-expressions-of-cyp2a7-mia-and-mia-rab4b-lncrna-and-contributes-to-fap-like-phenotype-in-apc-mutation-negative-familial-colorectal-cancer-patients
#8
Lai Fun Thean, Yu Hui Wong, Michelle Lo, Carol Loi, Min Hoe Chew, Choong Leong Tang, Peh Yean Cheah
Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. Our ability to exhaustively screen for APC mutations identify microsatellite-stable and APC-mutation negative familial CRC patients, enabling us to search for novel genes. We performed genome-wide scan on two affected siblings of one family and 88 ethnicity- and gender-matched healthy controls to identify deletions shared by the siblings. Combined loss of heterozygosity, copy number and allelic-specific copy number analysis uncovered 5 shared deletions...
2017: PloS One
https://www.readbyqxmd.com/read/28301736/epigenetic-regulation-a-new-frontier-for-biomedical-engineers
#9
Zhen Chen, Shuai Li, Shankar Subramaniam, John Y-J Shyy, Shu Chien
Gene expression in mammalian cells depends on the epigenetic status of the chromatin, including DNA methylation, histone modifications, promoter-enhancer interactions, and noncoding RNA-mediated regulation. The coordinated actions of these multifaceted regulations determine cell development, cell cycle regulation, cell state and fate, and the ultimate responses in health and disease. Therefore, studies of epigenetic modulations are critical for our understanding of gene regulation mechanisms at the molecular, cellular, tissue, and organ levels...
March 6, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28301256/sperm-epigenetics-in-the-study-of-male-fertility-offspring-health-and-potential-clinical-applications
#10
Timothy G Jenkins, Kenneth I Aston, Emma R James, Douglas T Carrell
The mammalian sperm contains a highly unique and specialized epigenetic landscape that offers a great degree of interesting research opportunities. One key discriminating feature of the mature sperm epigenome is that it, in theory, represents both remnant marks used throughout spermatogenesis to generate sperm cells competent to perform their function, but also marks that appear to be useful beyond fertilization. Key questions must be asked about the utility of these marks and the multiple purposes that may be served...
April 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/28300839/bidirectional-transcription-of-linc00441-and-rb1-via-h3k27-modification-dependent-way-promotes-hepatocellular-carcinoma
#11
Junwei Tang, Yu Xie, Xiaoliang Xu, Yin Yin, Runqiu Jiang, Lei Deng, Zhongming Tan, Venkatanarayana Gangarapu, Jinhai Tang, Beicheng Sun
The retinoblastoma gene (RB1), a known tumor-suppressor gene (TSG), was decreased in multiple cancers including hepatocellular carcinoma (HCC). Here we focused on the bidirectional transcripted long noncoding RNA (Linc00441) with neighbor gene RB1 to investigate whether Linc00441 is involved in the suppression of RB1 in HCC. We found that aberrant upregulated intranuclear Linc00441 was reversely correlated with RB1 expression in human HCC samples. The gain- and loss-of-function investigation revealed that Linc00441 could promote the proliferation of HCC cells in vitro and in vivo with an apoptosis suppression and cell cycle rearrangement...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28297619/clinical-implications-of-genetic-mutations-in-myelodysplastic-syndrome
#12
James A Kennedy, Benjamin L Ebert
Myelodysplastic syndrome (MDS) is clonal disorder characterized by ineffective hematopoiesis and a tendency to evolve into acute myeloid leukemia (AML). Genetic studies have enabled the identification of a set of recurrently mutated genes central to the pathogenesis of MDS, which can be organized into a limited number of cellular processes, including RNA splicing, epigenetic and traditional transcriptional regulation, and signal transduction. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis to frank MDS, and, ultimately, to secondary AML...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28293170/an-insight-into-the-increasing-role-of-lncrnas-in-the-pathogenesis-of-gliomas
#13
REVIEW
Yuanliang Yan, Zhijie Xu, Zhi Li, Lunquan Sun, Zhicheng Gong
Long non-coding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of gliomas are not fully understood. With the development of deep sequencing analyses, an extensive amount of functional non-coding RNAs has been discovered in glioma tissues and cell lines. Additionally, the contributions of several lncRNAs, such as Hox transcript antisense intergenic RNA, H19 and Colorectal neoplasia differentially expressed, previously reported to be involved in other pathogenesis and processes to the oncogenesis of glioblastoma are currently addressed...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28292312/comprehensive-discovery-of-subsample-gene-expression-components-by-information-explanation-therapeutic-implications-in-cancer
#14
Shirley Pepke, Greg Ver Steeg
BACKGROUND: De novo inference of clinically relevant gene function relationships from tumor RNA-seq remains a challenging task. Current methods typically either partition patient samples into a few subtypes or rely upon analysis of pairwise gene correlations that will miss some groups in noisy data. Leveraging higher dimensional information can be expected to increase the power to discern targetable pathways, but this is commonly thought to be an intractable computational problem. METHODS: In this work we adapt a recently developed machine learning algorithm for sensitive detection of complex gene relationships...
March 15, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28291707/epigenetics-of-atherosclerosis-emerging-mechanisms-and-methods
#15
REVIEW
Nadiya Khyzha, Azad Alizada, Michael D Wilson, Jason E Fish
Atherosclerosis is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls. Vessel occlusion, often occurring after plaque rupture, can result in myocardial and cerebral infarction. Epigenetic changes are increasingly being associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. Emerging genomic approaches that profile DNA methylation, chromatin accessibility, post-translational histone modifications, transcription factor binding, and RNA expression in low or single cell populations are poised to enhance our spatiotemporal understanding of atherogenesis...
March 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#16
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not appreciably established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28285723/epigenetic-aspects-of-rheumatoid-arthritis-contribution-of-non-coding-rnas
#17
REVIEW
Bogdan Kolarz, Maria Majdan
Since microRNA was discovered in the late 1990s the role of non-coding RNAs in the regulation of cellular processes has been confirmed. Intensive researches have revealed a number of subtypes of non-coding RNA. It has been proved that these molecules can influence each step of the development of cells and tissues. Moreover, researchers have found their expression change during disease development. In this article, we gathered the current results on the contribution of microRNA and long non-coding RNA in rheumatoid arthritis pathogenesis and their potential use in rheumatoid arthritis treatment...
January 20, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28284523/demethylase-kdm6a-epigenetically-promotes-il-6-and-ifn-%C3%AE-production-in-macrophages
#18
Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown...
March 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28282384/adaptation-of-a-to-i-rna-editing-in-drosophila
#19
Yuange Duan, Shengqian Dou, Shiqi Luo, Hong Zhang, Jian Lu
Adenosine-to-inosine (A-to-I) editing is hypothesized to facilitate adaptive evolution by expanding proteomic diversity through an epigenetic approach. However, it is challenging to provide evidences to support this hypothesis at the whole editome level. In this study, we systematically characterized 2,114 A-to-I RNA editing sites in female and male brains of D. melanogaster, and nearly half of these sites had events evolutionarily conserved across Drosophila species. We detected strong signatures of positive selection on the nonsynonymous editing sites in Drosophila brains, and the beneficial editing sites were significantly enriched in genes related to chemical and electrical neurotransmission...
March 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28280365/downregulation-of-long-noncoding-rna-hotairm1-promotes-monocyte-dendritic-cell-differentiation-through-competitively-binding-to-endogenous-mir-3960
#20
Jiaxuan Xin, Jing Li, Yue Feng, Liyang Wang, Yuan Zhang, Rongcun Yang
Myeloid differentiation is controlled by a multilayered regulatory circuitry consisting of various elements, including histone modifications, transcription factors, and posttranscriptional regulators such as miRNAs, long noncoding RNAs, and circular RNAs. However, the molecular mechanism underlying this biological process remains unclear. In this study, through epigenetic profiling analysis using chromatin immunoprecipitation (ChIP) followed by sequencing (ChIP-seq), we identified an lncRNA, HOTAIRM1, with a critical role in myeloid development...
2017: OncoTargets and Therapy
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