Cancer initiation and progression are caused by "driver" mutations that are vastly outnumbered by the "passenger" mutations that accumulate due to cancer-associated genome instability. With genome-...
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ISBN:
(纸本)9781450342254
Cancer initiation and progression are caused by "driver" mutations that are vastly outnumbered by the "passenger" mutations that accumulate due to cancer-associated genome instability. With genome-wide detection of somatic mutations now becoming commonplace for moderate-sized cancer studies, improvements in methods for discriminating driver from passenger mutations would significantly advance the field of cancer biology. In large-cohort studies, recurrence of mutations within a regulatory element can be used to identify probable driver mutations;but for small-cohort studies of new cancer types or subtypes, the recurrence approach by itself has limited statistical power. In such cases, bioinformatic approaches work well for functional assessment of somatic mutations within protein-coding genes, but how to functionally assess noncoding somatic mutations-using large-scale datasets of measurements and information about the local genomic context of the mutation-is a fundamental open problem in bioinformatics. Based on recent reports of specific noncoding mutations that drive cancer progression, we proposed and investigated a recurrence-based regression approach for quantifying the cancer-promoting potential of the local genomic and chromatin context of a somatic mutation. We integrated 29 genomic correlates (from sequence conservation, sequence GC content, distance to the nearest gene, and ENCODE project genome location datasets) within seven different regression models in three model classes (generalized linear models (GLMs), ensemble decision tree models, and neural network models). We trained and tested the models using a combined dataset of 4.5 million noncoding somatic mutations from 20 different types of cancer. We then characterized the models' accuracies and obtained relative importance scores for the features. We found that the Poisson regression model performs the best among the regression models and that a deep neural network structure is promising for predict
Humans may share more genomic commonalities with other species than previously thought. According to current estimates, ~5% of the human genome is functionally constrained, which is a much larger fraction than the ~1....
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Micro RNAs(mi RNAs) are small,noncoding RNA molecules that regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncoding RNAs(lnc RNAs),another class of noncoding RNAs,have been ...
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Micro RNAs(mi RNAs) are small,noncoding RNA molecules that regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncoding RNAs(lnc RNAs),another class of noncoding RNAs,have been determined to be also involved in transcription regulation and translation of target genes. Since deregulated expression levels or functions of miR NAs and lncR NAs in hepatocellular carcinoma(HCC) are frequently observed,clinical use of noncoding RNAs for novel diagnostic and therapeutic applications in the management of HCCs is highly and emergently e xpe c t e d. H e r e,we s ummar iz e r e c e nt f indings regarding deregulated mi RNAs and lnc RNAs for their potential clinical use as diagnostic and prognostic biomarkers of HCC. Specifically,we emphasize the deregulated expression levels of such noncoding RNAs in patients' sera as noninvasive biomarkers,a field that requires urgent improvement in the clinical surveillance of HCC. Since nucleotide-based strategies are being applied to clinical therapeutics,we further summarize clinical and preclinical trials using oligonucleotides involving the use of miR NAs and small interfering RNAs against HCC as novel therapeutics. Finally,we discuss current open questions,which must be clarified in the near future for realistic clinical applications of these new strategies.
noncoding RNAs(nc RNAs) represent a class of RNA molecules that typically do not code for proteins. Emerging data suggest that nc RNAs play an important role in several physiological and pathological conditions such a...
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noncoding RNAs(nc RNAs) represent a class of RNA molecules that typically do not code for proteins. Emerging data suggest that nc RNAs play an important role in several physiological and pathological conditions such as cancer. The best-characterized nc RNAs are the micro RNAs(mi RNAs), which are short, approximately 22-nucleotide sequences of RNA of approximately 22-nucleotide in length that regulate gene expression at the posttranscriptional level, through transcript degradation or translational repression. Mi RNAs can function as master gene regulators, impacting a variety of cellular pathways important to normal cellular functions as well as cancer development and progression. In addition to mi RNAs, long nc RNAs, which are transcripts longer than 200 nucleotides, have recently emerged as novel drivers of tumorigenesis. However, the molecular mechanisms of their regulation and function, and the significance of other nc RNAs such as piwi-interacting RNAs in pancreas carcinogenesis are largely unknown. This review summarizes the growing body of evidence supporting the vital roles of nc RNAs in pancreatic cancer, focusing on their dysregulation through both genetic and epigenetic mechanisms, and highlighting the promise of nc RNAs in diagnostic and therapeutic applications of pancreatic cancer.
Long noncoding Rnas in Imprinting and X Chromosome Inactivation. by Autuoro, Joseph M.; Pirnie, Stephan P.; Carmichael, Gordon G.; Autuoro, Joseph M.; Pirnie, Stephan P.; Carmichael, Gordon G.; published by
Long noncoding Rnas in Imprinting and X Chromosome Inactivation. by Autuoro, Joseph M.; Pirnie, Stephan P.; Carmichael, Gordon G.; Autuoro, Joseph M.; Pirnie, Stephan P.; Carmichael, Gordon G.; published by
Vitiligo is a prevailing disfiguring skin disorder characterized by the selective absence of functional melanocytes,affecting 0.5%to 1%of the global population.^([1])Several hypotheses have been proposed for its patho...
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Vitiligo is a prevailing disfiguring skin disorder characterized by the selective absence of functional melanocytes,affecting 0.5%to 1%of the global population.^([1])Several hypotheses have been proposed for its pathogenesis,including autoimmunity,oxidative stress,genetic and environmental factors,and metabolic abnormalities.^([2])No individual factor can completely explain the complex progression of this *** of the human genome encodes RNAs that are not translated into proteins,termed noncoding RNAs(ncRNAs).
AIM: To study the expression of long noncoding RNAs(lncRNAs) in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).METHODS: The lncRNA profiles between HBV-related HCC tissues and corresponding normal liver ...
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AIM: To study the expression of long noncoding RNAs(lncRNAs) in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).METHODS: The lncRNA profiles between HBV-related HCC tissues and corresponding normal liver tissues were generated using microarray analysis. Datasets were analyzed using multiple algorithms to depict alterations in gene expression on the basis of gene ontology(GO), pathway analysis, and lncRNA ***: The microarray revealed that 1772 lncRNAs and 2508 mRNAs were differently expressed. The pathway analysis demonstrated that the cell cycle, cytokinecytokine receptor interaction, chemokine signaling pathway, and phosphoinositide 3-kinase-protein kinase B signaling pathway may play important roles in *** GO terms, such as cell cycle, DNA replication,immune response, and signal transduction, were enriched in gene lists, suggesting a potential correlation with HBVrelated HCC. The upregulated large intergenic noncoding RNA ULK4P2 was physically combined with enhancer of zeste homolog 2. Therefore, the lncRNAs may participate in regulating HBV-related ***: lncRNAs play important roles in HCC,future studies should verify whether large intergenic noncoding ULK4P2 functions by combining with enhancer of zeste homolog 2 in HCC.
Objective To explore the expression and clinicalpathological significance of long non-coding transcriptionfactor 7 ( lncTCF7) in gastric cancer tissues and to investigatethe role of lncTCF7 in the invasion and metasta...
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Objective To explore the expression and clinicalpathological significance of long non-coding transcriptionfactor 7 ( lncTCF7) in gastric cancer tissues and to investigatethe role of lncTCF7 in the invasion and metastasisof gastric cancer by in vitro experimental *** From January to June 2011,one hundred patientswith gastric cancer who underwent radical gastrectomywere selected from Renji Hospital Affiliated toShanghai Jiaotong University School of Medicine. Theexpression of lncTCF7 at mRNA level was detected byquantitative real-time polymerase chain reaction ( qRTPCR).The patients were divided into high expressiongroup (50 cases) and low expression group (50 cases)according to the lncTCF7 mRNA expression level. Thestable interferenced lncTCF7 cell line ( stable interferencegroup) and blank control lncTCF7 cell line (blankcontrol group) were established. Then the relationshipbetween lncTCF7 expression level and clinical pathologicalcharacteristics and prognosis was analyzed.
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