Network analysis of ChIP-Seq data reveals key genes in prostate cancer
EUROPEAN JOURNAL OF MEDICAL RESEARCH
Authors: Zhang, Yu; Huang, Zhen; Zhu, Zhiqiang; Liu, Jianwei; Zheng, Xin; Zhang, Yuhai
Abstract
Background: Prostate cancer (PC) is the second most common cancer among men in the United States, and it imposes a considerable threat to human health. A deep understanding of its underlying molecular mechanisms is the premise for developing effective targeted therapies. Recently, deep transcriptional sequencing has been used as an effective genomic assay to obtain insights into diseases and may be helpful in the study of PC. Methods: In present study, ChIP-Seq data for PC and normal samples were compared, and differential peaks identified, based upon fold changes (with P-values calculated with t-tests). Annotations of these peaks were performed. Protein-protein interaction (PPI) network analysis was performed with BioGRID and constructed with Cytoscape, following which the highly connected genes were screened. Results: We obtained a total of 5,570 differential peaks, including 3,726 differentially enriched peaks in tumor samples and 1,844 differentially enriched peaks in normal samples. There were eight significant regions of the peaks. The intergenic region possessed the highest score (51%), followed by intronic (31%) and exonic (11%) regions. The analysis revealed the top 35 highly connected genes, which comprised 33 differential genes (such as YWHAQ, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein and. polypeptide) from ChIP-Seq data and 2 differential genes retrieved from the PPI network: UBA52 (ubiquitin A-52 residue ribosomal protein fusion product 1) and SUMO2 (SMT3 suppressor of mif two 3 homolog 2). Conclusions: Our findings regarding potential PC-related genes increase the understanding of PC and provides direction for future research.
A 14-3-3 mRNA is up-regulated in amyotrophic lateral sclerosis spinal cord
JOURNAL OF NEUROCHEMISTRY
Authors: Malaspina, A; Kaushik, N; de Belleroche, J
Abstract
We have recently isolated a 2.2-kb cDNA clone (1C5) from a human spinal cord cDNA library with partial identity to the 14-3-3 protein mRNA encoding the a protein (YWHAQ). 14-3-3 protein transcripts are highly expressed in large projection neurones of the hippocampus, cerebellum, and spinal cord and have been found to be significantly up-regulated in rat motor neurones following hypoglossal nerve axotomy. In this study we investigated whether the 1C5 transcript (YWHAQ) isolated from spinal cord was involved in amyotrophic lateral sclerosis (ALS). We found a significant up-regulation of 1C5 (YWHAQ) in lumbar spinal cord from patients with sporadic ALS compared with controls, with the highest levels of expression being found in individuals with predominant lower motor neurone involvement. A 6-bp tandem repeat in the 5'-untranslated region of the gene was found to be polymorphic, but no significant association with disease was found following genomic analysis of this region. The localisation of 1C5 (YWHAQ) to chromosome 2 was determined and coincides with that reported for clone HS1 (EMBL accession no. X57347), These results show the marked up-regulation of the 14-3-3 isoform (YWHAQ) in ALS spinal cord and indicate the involvement of a potential 14-3-3-mediated survival pathway in the pathogenesis of ALS.