scholarly journals An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes

2021 ◽  
Vol 22 (21) ◽  
pp. 11481
Author(s):  
Heike Thiemeyer ◽  
Leila Taher ◽  
Jan Torben Schille ◽  
Eva-Maria Packeiser ◽  
Lisa K. Harder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Malignant Disease ◽  
Pi3k Signaling ◽  
Rna Seq ◽  
Promising Candidate ◽  
Fine Needle ◽  
Human Counterpart ◽  
Transcriptional Landscape

Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the transcriptional landscape of canine PCa and the identification of diagnostic, prognostic and/or therapeutic biomarkers through a multi-step screening approach. RNA-Sequencing of ten malignant tissues and fine-needle aspirations (FNA), and 14 nonmalignant tissues and FNAs was performed to find differentially expressed genes (DEGs) and deregulated pathways. The 4098 observed DEGs were involved in 49 pathways. These 49 pathways could be grouped into five superpathways summarizing the hallmarks of canine PCa: (i) inflammatory response and cytokines; (ii) regulation of the immune system and cell death; (iii) cell surface and PI3K signaling; (iv) cell cycle; and (v) phagosome and autophagy. Among the highly deregulated, moderately to strongly expressed DEGs that were members of one or more superpathways, 169 DEGs were listed in relevant databases and/or the literature and included members of the PCa pathway, oncogenes, prostate-specific genes, and druggable genes. These genes are novel and promising candidate diagnostic, prognostic and/or therapeutic canine PCa biomarkers.

scholarly journals Unexpected mutual regulation underlies paralogue functional diversification and promotes epithelial tissue maturation in Tribolium

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Daniela Gurska ◽  
Iris M. Vargas Jentzsch ◽  
Kristen A. Panfilio
Keyword(s):  
Feedback Loop ◽  
Single Species ◽  
Epithelial Tissue ◽  
Rna Seq ◽  
Developmental Progression ◽  
Late Embryogenesis ◽  
Mutual Regulation ◽  
Transcriptional Landscape

Abstract Insect Hox3/zen genes represent an evolutionary hotspot for changes in function and copy number. Single orthologues are required either for early specification or late morphogenesis of the extraembryonic tissues, which protect the embryo. The tandemly duplicated zen paralogues of the beetle Tribolium castaneum present a unique opportunity to investigate both functions in a single species. We dissect the paralogues’ expression dynamics (transcript and protein) and transcriptional targets (RNA-seq after RNAi) throughout embryogenesis. We identify an unexpected role of Tc-Zen2 in repression of Tc-zen1, generating a negative feedback loop that promotes developmental progression. Tc-Zen2 regulation is dynamic, including within co-expressed multigene loci. We also show that extraembryonic development is the major event within the transcriptional landscape of late embryogenesis and provide a global molecular characterization of the extraembryonic serosal tissue. Altogether, we propose that paralogue mutual regulation arose through multiple instances of zen subfunctionalization, leading to their complementary extant roles.

scholarly journals Unexpected mutual regulation underlies paralogue functional diversification and promotes maturation of a protective epithelial tissue

2018 ◽  
Author(s):  
Daniela Gurska ◽  
Iris M. Vargas Jentzsch ◽  
Kristen A. Panfilio
Keyword(s):  
Feedback Loop ◽  
Single Species ◽  
Epithelial Tissue ◽  
Rna Seq ◽  
Developmental Progression ◽  
Late Embryogenesis ◽  
Mutual Regulation ◽  
Transcriptional Landscape

ABSTRACTInsect Hox3/zen genes represent an evolutionary hotspot for changes in function and copy number. Single orthologues are required either for early specification or late morphogenesis of the extraembryonic tissues, which protect the embryo. The tandemly duplicated zen paralogues of the beetle Tribolium castaneum present a unique opportunity to investigate both functions in a single species. We dissect the paralogues’ expression dynamics (transcript and protein) and transcriptional targets (RNA-seq after RNAi) throughout embryogenesis. We identify an unexpected role of Tc-Zen2 in repression of Tc-zen1, generating a negative feedback loop that promotes developmental progression. Tc-Zen2 regulation is dynamic, including within co-expressed multigene loci. We also show that extraembryonic development is the major event within the transcriptional landscape of late embryogenesis and provide a global molecular characterization of the extraembryonic serosal tissue. Altogether, we propose that paralogue mutual regulation arose progressively and drove multiple instances of zen subfunctionalization, leading to complementary extant roles.

scholarly journals Transcriptional landscape of the human cell cycle

2017 ◽  
Vol 114 (13) ◽  
pp. 3473-3478 ◽  
Author(s):  
Yin Liu ◽  
Sujun Chen ◽  
Su Wang ◽  
Fraser Soares ◽  
Martin Fischer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Steady State ◽  
Histone Modification ◽  
Human Cell ◽  
Rna Seq ◽  
Motif Analysis ◽  
Chip Sequencing ◽  
Histone 3 ◽  
M Phase ◽  
Transcriptional Landscape

Steady-state gene expression across the cell cycle has been studied extensively. However, transcriptional gene regulation and the dynamics of histone modification at different cell-cycle stages are largely unknown. By applying a combination of global nuclear run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and histone-modification Chip sequencing (ChIP-seq), we depicted a comprehensive transcriptional landscape at the G0/G1, G1/S, and M phases of breast cancer MCF-7 cells. Importantly, GRO-seq and RNA-seq analysis identified different cell-cycle–regulated genes, suggesting a lag between transcription and steady-state expression during the cell cycle. Interestingly, we identified genes actively transcribed at early M phase that are longer in length and have low expression and are accompanied by a global increase in active histone 3 lysine 4 methylation (H3K4me2) and histone 3 lysine 27 acetylation (H3K27ac) modifications. In addition, we identified 2,440 cell-cycle–regulated enhancer RNAs (eRNAs) that are strongly associated with differential active transcription but not with stable expression levels across the cell cycle. Motif analysis of dynamic eRNAs predicted Kruppel-like factor 4 (KLF4) as a key regulator of G1/S transition, and this identification was validated experimentally. Taken together, our combined analysis characterized the transcriptional and histone-modification profile of the human cell cycle and identified dynamic transcriptional signatures across the cell cycle.

scholarly journals Characterization of epigenetic and transcriptional landscape in infantile hemangiomas with ATAC-seq and RNA-seq

Epigenomics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 893-905 ◽  
Author(s):  
Xueqing Li ◽  
Yuanzheng Chen ◽  
Cong Fu ◽  
Hongwen Li ◽  
Kun Yang ◽  
...  
Keyword(s):  
Opposite Effect ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Rna Seq ◽  
Epigenetic Landscape ◽  
Normal Tissues ◽  
Umbilical Vein Endothelial Cells ◽  
Accessible Chromatin ◽  
Transcriptional Landscape

Aim: This study was conducted to reveal epigenetic landscape in infantile hemangiomas (IHs) and identify transcription factors (TFs) and their downstream genes active in IHs. Materials & methods: We performed Assay for Transposase Accessible Chromatin (ATAC-seq) with RNA-seq in three pairs of IHs and their adjacent normal tissues. Functions of candidate TFs were investigated in human umbilical vein endothelial cells (HUVECs). Results: Chromatin of IH tissues is less compact. Some candidate genes and TFs were identified. In HUVECs, SPDEF inhibited cell viability and tube formation, and promoted apoptosis; SOX4 exerted the opposite effect. SPDEF may act through EPHA5, ZBTB46 and SASH1; SOX4 may act through MMP12 and HIVEP3. Conclusion: Epigenetics plays a role in IHs. SPDEF and SOX4 may act in IHs.

scholarly journals Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq

2011 ◽  
Vol 21 (7) ◽  
pp. 1160-1167 ◽  
Author(s):  
S. Islam ◽  
U. Kjallquist ◽  
A. Moliner ◽  
P. Zajac ◽  
J.-B. Fan ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Seq ◽  
Transcriptional Landscape

scholarly journals Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle–Related Transcription and Attenuated Androgen Response

2017 ◽  
Vol 78 (4) ◽  
pp. 853-864 ◽  
Author(s):  
Aaron M. Horning ◽  
Yao Wang ◽  
Che-Kuang Lin ◽  
Anna D. Louie ◽  
Rohit R. Jadhav ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Single Cell ◽  
Cancer Cells ◽  
Rna Seq ◽  
Prostate Cancer Cells ◽  
Attenuated Androgen

scholarly journals Universal alternative splicing of noncoding exons

2017 ◽  
Author(s):  
Ira W. Deveson ◽  
Marion E. Brunck ◽  
James Blackburn ◽  
Elizabeth Tseng ◽  
Ting Hon ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Single Molecule ◽  
Gene Evolution ◽  
Rna Seq ◽  
Protein Coding ◽  
Noncoding Exon ◽  
Mouse Cells ◽  
Lower Limits ◽  
Transcriptional Landscape

The human transcriptome is so large, diverse and dynamic that, even after a decade of investigation by RNA sequencing (RNA-Seq), we are yet to resolve its true dimensions. RNA-Seq suffers from an expression-dependent bias that impedes characterization of low-abundance transcripts. We performed targeted single-molecule and short-read RNA-Seq to survey the transcriptional landscape of a single human chromosome (Hsa21) at unprecedented resolution. Our analysis reaches the lower limits of the transcriptome, identifying a fundamental distinction between protein-coding and noncoding gene content: almost every noncoding exon undergoes alternative splicing, producing a seemingly limitless variety of isoforms. Analysis of syntenic regions of the mouse genome shows that few noncoding exons are shared between human and mouse, yet human splicing profiles are recapitulated on Hsa21 in mouse cells, indicative of regulation by a deeply conserved splicing code. We propose that noncoding exons are functionally modular, with alternative splicing generating an enormous repertoire of potential regulatory RNAs and a rich transcriptional reservoir for gene evolution.

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