Transcriptome Profiling of the Cancer, Adjacent Non-Tumor and Distant Normal Tissues from a Colorectal Cancer Patient by Deep Sequencing

Wu, Yanan; Wang, Xuetao; Fangbo, Wu; Huang, Ruolei; Xue, Fangqin; Liang, Guantao; Tao, Min; Cai, Peng; Huang, Yi

doi:10.1371/journal.pone.0041001

Cited by 69 publications

(47 citation statements)

References 73 publications

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“…1D and 1E). For this purpose, we generated RNA-seq data from normal breast epithelial cells (NBE) grown briefly in culture (GSE74417), and downloaded published RNA-seq data from normal colon (NC, GSM835561 (40)), and promyelocytes (PME, GSM1704844 (41)). Genes regulated by DAC had lower expression in cancer (YB5, MCF7, HL60) compared to its expression in normal tissue (NC, NBE, PME) (Student’s t-test, p < 0.05), while genes regulated by Depsi did not show this decrease (Student’s t-test, p > 0.05) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Selectivity of Epigenetic Therapy in Cancer

et al. 2017

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A central challenge in the development of epigenetic cancer therapy is the ability to direct selectivity in modulating gene expression for disease-selective efficacy. To address this issue, we characterized by RNA-seq, DNA methylation and ChIP-seq analyses the epigenetic response of a set of colon, breast and leukemia cancer cell lines to small molecule inhibitors against DNA methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2 inhibitor GSK343). We also characterized the effects of DAC as combined with the other compounds. Averaged over the cancer cell models employed, we found that DAC affected 8.6% of the transcriptome and that 95.4% of the genes affected were upregulated. DAC preferentially regulated genes that were silenced in cancer and that were methylated at their promoters. In contrast, Depsi affected the expression of 30.4% of the transcriptome but showed little selectivity for gene upregulation or silenced genes. S2101, UNC0638, and GSK343 affected only 2% of the transcriptome, with UNC0638 and GSK343 preferentially targeting genes marked with H3K9me2 or H3K27me3, respectively. When combined with histone methylase inhibitors, the extent of gene upregulation by DAC was extended while still maintaining selectivity for DNA methylated genes and silenced genes. However, the genes upregulated by combination treatment exhibited limited overlap, indicating the possibility of targeting distinct sets of genes based on different epigenetic therapy combinations. Overall, our results demonstrated that DNA methyltransferase inhibitors preferentially target cancer-relevant genes and can be combined with inhibitors targeting histone methylation for synergistic effects while still maintaining selectivity.

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Section: Resultsmentioning

confidence: 99%

Transcriptional Selectivity of Epigenetic Therapy in Cancer

et al. 2017

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“…In addition, Drosophila APC1 binds actin monomers, nucleates F-actin assembly (Jaiswal et al, 2013) and binds the microtubule plus-tip protein EB1 (Webb et al, 2009), like vertebrate APC. Previous studies have examined the global cellular consequence of APC disruption using RNA-seq and two-dimensional difference gel electrophoresis (2D-DIGE) proteomics (Chafey et al, 2009;Wu et al, 2012). However, the results of these studies reflect chronic changes due to the primary and downstream effects of ligand-independent Wnt target gene activation.…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis reveals APC-dependent post translational modifications and identifies a novel regulator of β-catenin

et al. 2016

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Wnt signaling generates patterns in all embryos, from flies to humans, and controls cell fate, proliferation and metabolic homeostasis. Inappropriate Wnt pathway activation results in diseases, including colorectal cancer. The adenomatous polyposis coli (APC) tumor suppressor gene encodes a multifunctional protein that is an essential regulator of Wnt signaling and cytoskeletal organization. Although progress has been made in defining the role of APC in a normal cellular context, there are still significant gaps in our understanding of APC-dependent cellular function and dysfunction. We expanded the APC-associated protein network using a combination of genetics and a proteomic technique called twodimensional difference gel electrophoresis (2D-DIGE). We show that loss of Drosophila Apc2 causes protein isoform changes reflecting misregulation of post-translational modifications (PTMs), which are not dependent on β-catenin transcriptional activity. Mass spectrometry revealed that proteins involved in metabolic and biosynthetic pathways, protein synthesis and degradation, and cell signaling are affected by Apc2 loss. We demonstrate that changes in phosphorylation partially account for the altered PTMs in APC mutants, suggesting that APC mutants affect other types of PTM. Finally, through this approach Aminopeptidase P was identified as a new regulator of β-catenin abundance in Drosophila embryos. This study provides new perspectives on the cellular effects of APC that might lead to a deeper understanding of its role in development.

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“…For example, Sinicropi et al applied RNA-seq using FFPE samples to profile genome-wide mRNA expression in 136 breast cancer patients and identified 32 mRNAs that can serve as breast cancer biomarkers, indicating that RNA-Seq can provide a practical, sensitive and precise platform for genome-wide biomarker discovery in FFPE tissue. Similarly, RNA-seq has been applied to study biomarkers in hepatocellular carcinoma [137] , colorectal cancer [138] , B-cell lymphoma [139] , melanoma [140] , and prostate cancer [141] . RNA-seq has also been used to analyze alternative splicing associated in lung cancer [142] .…”

Section: Mrna Profiles As Diagnostic Cancer Markersmentioning

confidence: 99%

Genome-wide analysis of microRNA and mRNA expression signatures in cancer

Xiao

2015

Acta Pharmacol Sin

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Cancer is an extremely diverse and complex disease that results from various genetic and epigenetic changes such as DNA copy-number variations, mutations, and aberrant mRNA and/or protein expression caused by abnormal transcriptional regulation. The expression profiles of certain microRNAs (miRNAs) and messenger RNAs (mRNAs) are closely related to cancer progression stages. In the past few decades, DNA microarray and next-generation sequencing techniques have been widely applied to identify miRNA and mRNA signatures for cancers on a genome-wide scale and have provided meaningful insights into cancer diagnosis, prognosis and personalized medicine. In this review, we summarize the progress in genome-wide analysis of miRNAs and mRNAs as cancer biomarkers, highlighting their diagnostic and prognostic roles.

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Transcriptome Profiling of the Cancer, Adjacent Non-Tumor and Distant Normal Tissues from a Colorectal Cancer Patient by Deep Sequencing

Cited by 69 publications

References 73 publications

Transcriptional Selectivity of Epigenetic Therapy in Cancer

Transcriptional Selectivity of Epigenetic Therapy in Cancer

Proteomic analysis reveals APC-dependent post translational modifications and identifies a novel regulator of β-catenin

Genome-wide analysis of microRNA and mRNA expression signatures in cancer

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