scholarly journals Integrated Analysis Reveals hsa-miR-142 as a Representative of a Lymphocyte-Specific Gene Expression and Methylation Signature

2012 ◽  
Vol 11 ◽  
pp. CIN.S9037 ◽  
Author(s):  
Bill Andreopoulos ◽  
Dimitris Anastassiou
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
Specific Gene ◽  
Data Types ◽  
Multiple Cancer ◽  
Specific Expression ◽  
Cancer Types ◽  
Cell Cell

Gene expression profiling has provided insights into different cancer types and revealed tissue-specific expression signatures. Alterations in microRNA expression contribute to the pathogenesis of many types of human diseases. Few studies have integrated all levels of gene expression, miRNA and methylation to uncover correlations between these data types. We performed an integrated profiling to discover instances of miRNAs associated with a gene expression and DNA methylation signature across multiple cancer types. Using data from The Cancer Genome Atlas (TCGA), we revealed a concordant gene expression and methylation signature associated with the microRNA hsa-miR-142 across the same samples. In all cancer types examined, we found a signature of co-expression of a gene set R and methylated sites M, which correlate positively (M+) or negatively (M–) with the expression of hsa-miR-142. The set R consistently contains many genes, such as TRAF3IP3, NCKAP1L, CD53, LAPTM5, PTPRC, EVI2B, DOCK2, LCP2, CYBB and FYB. The signature is preserved across glioblastoma, ovarian, breast, colon, kidney, lung, uterine and rectum cancer. There is 28% overlap of methylation sites in M between glioblastoma (GBM) and ovarian cancer. There is 60% overlap of genes in R between GBM and ovarian ( P = 1.3e−-11). Most of the genes in R are known to be expressed in lymphocytes and haematopoietic stem cells, while M reflects membrane proteins involved in cell-cell adhesion functions. We speculate that the hsa-miR-142 associated signature may signal haematopoietic-specific processes and an accumulation of methylation events triggering a progressive loss of cell-cell adhesion. We also observed that GBM samples belonging to the proneural subtype tend to have underexpressed hsa-miR-142 and R genes, hypomethylated M+ and hypermethylated M–, while the mesenchymal samples have the opposite profile.

scholarly journals Multi-omics characterization and validation of invasiveness-related molecular features across multiple cancer types

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Guoshu Bi ◽  
Jiaqi Liang ◽  
Yuansheng Zheng ◽  
Runmei Li ◽  
Mengnan Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Predictive Biomarker ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Multiple Cancer ◽  
Tumor Invasiveness ◽  
Molecular Features ◽  
Cancer Types

Abstract Background Tumor invasiveness reflects many biological changes associated with tumorigenesis, progression, metastasis, and drug resistance. Therefore, we performed a systematic assessment of invasiveness-related molecular features across multiple human cancers. Materials and methods Multi-omics data, including gene expression, miRNA, DNA methylation, and somatic mutation, in approximately 10,000 patients across 30 cancer types from The Cancer Genome Atlas, Gene Expression Omnibus, PRECOG, and our institution were enrolled in this study. Results Based on a robust gene signature, we established an invasiveness score and found that the score was significantly associated with worse prognosis in almost all cancers. Then, we identified common invasiveness-associated dysregulated molecular features between high- and low-invasiveness score group across multiple cancers, as well as investigated their mutual interfering relationships thus determining whether the dysregulation of invasiveness-related genes was caused by abnormal promoter methylation or miRNA expression. We also analyzed the correlations between the drug sensitivity data from cancer cell lines and the expression level of 685 invasiveness-related genes differentially expressed in at least ten cancer types. An integrated analysis of the correlations among invasiveness-related genetic features and drug response were conducted in esophageal carcinoma patients to outline the complicated regulatory mechanism of tumor invasiveness status in multiple dimensions. Moreover, functional enrichment suggests the invasiveness score might serve as a predictive biomarker for cancer patients receiving immunotherapy. Conclusion Our pan-cancer study provides a comprehensive atlas of tumor invasiveness and may guide more precise therapeutic strategies for tumor patients.

Cdx1 or Cdx2 expression activates E-cadherin-mediated cell-cell adhesion and compaction in human COLO 205 cells

2004 ◽  
Vol 287 (1) ◽  
pp. G104-G114 ◽  
Author(s):  
Matthew S. Keller ◽  
Toshihiko Ezaki ◽  
Rong-Jun Guo ◽  
John P. Lynch
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Gene Expression Pattern ◽  
Cell Junctions ◽  
Specific Gene ◽  
Specific Response ◽  
Specific Gene Expression ◽  
Cdx2 Expression ◽  
E Cadherin ◽  
Cell Cell

A mature columnar intestinal epithelium develops late in embryogenesis and is maintained throughout the life of the organism. Although the mechanisms driving intestine-specific gene expression have been well studied, those promoting the acquisition of cell-cell junctions, columnar morphogenesis, and polarization have been less studied. The Cdx homeodomain transcription factors (Cdx1 and Cdx2) regulate intestine-specific gene expression and intestinal epithelial differentiation. We report here that Cdx expression induces E-cadherin activity and cell-cell adhesion in human COLO 205 cancer cells. Within days of Cdx1 or Cdx2 expression, a new homotypic cell-cell adhesion phenotype is induced. This is a specific response to Cdx, inasmuch as a Cdx1 mutant failed to elicit the effect. Additionally, Cdx-expressing COLO 205 cells demonstrate a reduced proliferative capacity and an increase in the mRNA expression of differentiation-associated genes. Electron micrographs of these cells demonstrate induction of tight, adherens, and desmosomal junctions, as well as a columnar shape and apical microvilli. Investigations of the adhesion phenotype determined that it was Ca2+dependent and could be blocked by an E-cadherin-blocking antibody. However, E-cadherin protein levels and intracellular distribution were unchanged. Cdx expression restored the ability of the cell membranes to adhere and undergo compaction. We conclude that Cdx1 or Cdx2 expression is sufficient to induce an E-cadherin-dependent adhesion of COLO 205 cells. This adhesion is associated with polarization and cell-cell membrane compaction, as well as induction of a differentiated gene-expression pattern. Ascertaining the mechanism for this novel Cdx effect may yield insight into the development of mature colonic epithelium.

scholarly journals Pan-cancer driver copy number alterations identified by joint expression/CNA data analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gaojianyong Wang ◽  
Dimitris Anastassiou
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Multiple Cancer ◽  
Cancer Driver ◽  
Large Gene ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Pan Cancer

Abstract Analysis of large gene expression datasets from biopsies of cancer patients can identify co-expression signatures representing particular biomolecular events in cancer. Some of these signatures involve genomically co-localized genes resulting from the presence of copy number alterations (CNAs), for which analysis of the expression of the underlying genes provides valuable information about their combined role as oncogenes or tumor suppressor genes. Here we focus on the discovery and interpretation of such signatures that are present in multiple cancer types due to driver amplifications and deletions in particular regions of the genome after doing a comprehensive analysis combining both gene expression and CNA data from The Cancer Genome Atlas.

scholarly journals The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma

2021 ◽  
Author(s):  
Ekaterina Bourova-Flin ◽  
Samira Derakhshan ◽  
Afsaneh Goudarzi ◽  
Tao Wang ◽  
Anne-Laure Vitte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Specific Gene ◽  
Specific Expression ◽  
Intrinsic Nature ◽  
Independent Cohort

Abstract Background Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. Methods A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. Results A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. Discussion The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.

scholarly journals BART Cancer: a web resource for transcriptional regulators in cancer genomes

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Zachary V Thomas ◽  
Zhenjia Wang ◽  
Chongzhi Zang
Keyword(s):  
Gene Expression ◽  
Cancer Research ◽  
Computational Prediction ◽  
Transcriptional Regulators ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Regulation Of Transcription ◽  
Data Resource ◽  
Web Resource ◽  
Cancer Types

Abstract Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators, including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic profiles of active transcriptional regulators from primary cancer samples are limited in the public domain. Here we present BART Cancer (bartcancer.org), an interactive web resource database to display the putative transcriptional regulators that are responsible for differentially regulated genes in 15 different cancer types in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10000 gene expression profiling RNA-seq datasets from TCGA with over 7000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting the transcriptional regulators from the differentially expressed genes in cancer samples compared to normal samples. BART Cancer also displays the activities of over 900 transcriptional regulators across cancer types, by integrating computational prediction results from BART and the Cistrome Cancer database. Focusing on transcriptional regulator activities in human cancers, BART Cancer can provide unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities.

scholarly journals Methylation of the Cyclin A1 Promoter Correlates with Gene Silencing in Somatic Cell Lines, while Tissue-Specific Expression of Cyclin A1 Is Methylation Independent

2000 ◽  
Vol 20 (9) ◽  
pp. 3316-3329 ◽  
Author(s):  
Carsten Müller ◽  
Carol Readhead ◽  
Sven Diederichs ◽  
Gregory Idos ◽  
Rong Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Promoter Methylation ◽  
Cpg Island ◽  
Trichostatin A ◽  
Specific Gene ◽  
Cyclin A1 ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

ABSTRACT Gene expression in mammalian organisms is regulated at multiple levels, including DNA accessibility for transcription factors and chromatin structure. Methylation of CpG dinucleotides is thought to be involved in imprinting and in the pathogenesis of cancer. However, the relevance of methylation for directing tissue-specific gene expression is highly controversial. The cyclin A1 gene is expressed in very few tissues, with high levels restricted to spermatogenesis and leukemic blasts. Here, we show that methylation of the CpG island of the human cyclin A1 promoter was correlated with nonexpression in cell lines, and the methyl-CpG binding protein MeCP2 suppressed transcription from the methylated cyclin A1 promoter. Repression could be relieved by trichostatin A. Silencing of a cyclin A1 promoter-enhanced green fluorescent protein (EGFP) transgene in stable transfected MG63 osteosarcoma cells was also closely associated with de novo promoter methylation. Cyclin A1 could be strongly induced in nonexpressing cell lines by trichostatin A but not by 5-aza-cytidine. The cyclin A1 promoter-EGFP construct directed tissue-specific expression in male germ cells of transgenic mice. Expression in the testes of these mice was independent of promoter methylation, and even strong promoter methylation did not suppress promoter activity. MeCP2 expression was notably absent in EGFP-expressing cells. Transcription from the transgenic cyclin A1 promoter was repressed in most organs outside the testis, even when the promoter was not methylated. These data show the association of methylation with silencing of the cyclin A1 gene in cancer cell lines. However, appropriate tissue-specific repression of the cyclin A1 promoter occurs independently of CpG methylation.

Stage-specific expression of a developmentally regulated gene in Dirofilaria immitis

1992 ◽  
Vol 66 (1) ◽  
pp. 62-67 ◽  
Author(s):  
S. Sun ◽  
T. Matsuura ◽  
K. Sugane
Keyword(s):  
Gene Expression ◽  
Cdna Clone ◽  
Dirofilaria Immitis ◽  
Mrna Level ◽  
Specific Antigen ◽  
Specific Gene ◽  
Developmentally Regulated ◽  
Specific Expression ◽  
Specific Gene Expression

ABSTRACTA previously reported cDNA clone encoding 34 kDa antigenic polypeptide of Dirofilaria immitis (λ cD34) was studied to elucidate the mechanism of stage-specific gene expression. The 34 kDa polypeptide was a larva-specific antigen and the mRNA was detectable in microfilariae but not in adult worms and eggs. The λ cD34 gene was not sex linked and was contained in the genome of D. immitis at each stage. The stage-specific expression of the developmentally regulated gene in D. immitis may be controlled primarily at the mRNA level.

scholarly journals Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

2020 ◽  
Author(s):  
Nil Aygün ◽  
Angela L. Elwell ◽  
Dan Liang ◽  
Michael J. Lafferty ◽  
Kerry E. Cheek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Risk Variants ◽  
Allele Specific ◽  
Cell Type Specific ◽  
Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

scholarly journals RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival

2022 ◽  
Vol 23 (1) ◽  
pp. 496
Author(s):  
Kenzui Taniue ◽  
Tanzina Tanu ◽  
Yuki Shimoura ◽  
Shuhei Mitsutomi ◽  
Han Han ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Viability ◽  
The Cancer Genome Atlas ◽  
Multiple Cancer ◽  
Pancreatic Cancer Cells ◽  
Cancer Cell Survival ◽  
Cellular Machinery ◽  
Cancer Types ◽  
Rna Exosome ◽  
Tumor Types

The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies’ datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells.

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