Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Identification of a Novel Angiogenesis and Tumor Suppressor Gene Rab25 in Esophageal Squamous Cell Carcinoma

ABSTRACT: Twelve clinical samples from human esophageal squamous cell carcinoma (ESCC) (seven tumors and five non-tumors) were sequenced using Illumina high-throughput sequencing and the RNA-Seq profiling was investigated with 1730 genes significantly differentially expressed. The gene Rab25 was found to be down-regulated in tumors (p-value < 1E-20) and identified as a novel candidate tumor suppressor gene. The down-regulation of Rab25 was examined in a large cohort of ESCC and non-tumor cases by qPCR and immunohistochemistry analyses. Aberrant methylation in the promoter region of Rab25 was studied by demethylation treatment with 5-aza-dC and bisulfite genomic sequencing (BGS). In order to assess the effect of Rab25 on tumor growth and angiogenesis, in vitro and in vivo functional studies in ESCC cell lines using lentiviral-based overexpression or knockdown models were also performed. 7 tumor and 5 normal samples

ORGANISM(S): Homo sapiens

SUBMITTER: Jessie Yun-juan Bao

PROVIDER: E-GEOD-32424 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Rab25 is a tumor suppressor gene with antiangiogenic and anti-invasive activities in esophageal squamous cell carcinoma.

Tong Man M Chan Kwok Wah KW Bao Jessie Y J JY Wong Kai Yau KY Chen Jin-Na JN Kwan Pak Shing PS Tang Kwan Ho KH Fu Li L Qin Yan-Ru YR Lok Si S Guan Xin-Yuan XY Guan Xin-Yuan XY Ma Stephanie S

Cancer research 20120918 22

Esophageal squamous cell carcinoma (ESCC), the major histologic subtype of esophageal cancer, is a devastating disease characterized by distinctly high incidences and mortality rates. However, there remains limited understanding of molecular events leading to development and progression of the disease, which are of paramount importance to defining biomarkers for diagnosis, prognosis, and personalized treatment. By high-throughout transcriptome sequence profiling of nontumor and ESCC clinical sam ...[more]

PMID: 22991305

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Project description:Background: Alternative polyadenylation (APA) is emerging as a widespread mechanism of gene regulation. The usage of APA sites allows a single gene to encode multiple mRNA transcripts with different 3'-untranslated region (3'UTR) lengths. Many disease processes reflect the importance of the regulation of APA site switching. The objective of this study was to explore the profiling of tandem APA sites in nasal polyps compared with nasal uncinate process mucosa. Methods: Sequencing of APA sites (SAPAS) based on second-generation sequencing technology was undertaken to investigate the use of tandem APA sites and identify gene expression patterns in samples from the nasal polyps and nasal uncinate process mucosa of two patients with chronic rhinosinusitis with nasal polyps. The findings of the SAPAS analysis were validated via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: First, the results showed a switching of 3'UTR lengths in nasal polyps compared with nasal uncinate process mucosa. From the two patients, 105 overlapping genes in the nasal polyps were switched to distal poly(A) sites, and 90 such genes were switched to proximal poly(A) sites. Several Gene Ontology terms were enriched in the list of genes with switched APA sites, including transcription regulation, cell cycle, apoptosis, and metabolism. Second, we detected genes that showed differential expression with at least a 3-fold difference between nasal polyp tissue and nasal uncinate process mucosa. Between the two sample types, 627 genes exhibited differential expression. The qRT-PCR results confirmed our SAPAS results. Conclusion: APA site-switching events of 3'UTRs are prevalent in nasal polyp tissue, and the regulation of gene expression mediated by APA may play an important role in the formation and persistence of nasal polyps. Our results may provide new insights into the possible pathophysiologic processes involved in nasal polyps. Investigate the use of tandem APA sites of 3'ends of mRNAs using second-generation sequencing technology.

Project description:Nutritional status influences feeding behaviors, food preferences and taste sensations. For example, zinc-deficient rats have been reported to show reduced and cyclic food intake patterns with increased preferences for NaCl. Although some impairments of the central nervous and endocrine systems have been speculated to be involved in these phenomena, the effects of short-term zinc deficiency on the brain have not been well examined to date. In this study, we performed a comprehensive analysis of the gene expression patterns in the rat diencephalon, which is a portion of the brain that includes the hypothalamus and thalamus, after short-term zinc deficiency and also during zinc recovery. The rats showed reduced and cyclic food intake patterns with increased salt preferences after a 10-day dietary zinc deficiency. A comparative analysis of their diencephalons using cDNA microarrays revealed that approximately 1% of the genes expressed in the diencephalons showed significantly altered expression levels. On the other hand, a 6-day zinc supplementation following the deprivation allowed for the recovery to initial food intake behaviors and salt preferences. The expression levels of most of the genes that had been altered by exposure to zinc deficient conditions were also recovered. These results show that feeding behaviors, taste preferences and gene expression patterns in the diencephalon respond quickly to changing zinc levels. This suggests that the gene expression changes observed in the diencephalon and the accompanying functional changes may be related to the development of deviations in feeding behaviors and increased preferences for NaCl in zinc-deficient rats. Four-week-old male Sprague-Dawley rats were purchased from Charles River Japan (Yokohama, Japan). Fifteen rats were individually housed in a stainless steel cage in a room with constant humidity at 22 Â± 1 Â°C under a 12 h light-dark cycle (lights on at 8:00). Zinc-deficient diets (# D19488M, Research Diets, New Brunswick, NJ, USA) were based on the AIN-93G diet and contained 0.6 mg zinc / 1000 g diet (Table 1). For the control zinc-sufficient diets, zinc sulfate supplements were provided with up to 30.0 mg zinc / 1000 g diet. Rats were fed the control diets ad libitum for 1 week for adaptation and then were divided into two groups matched for body weight. For the zinc-deficient experiment, rats in the ZD group (n =9) were allowed to eat the zinc-deficient diets ad libitum. The rats in the PF group (n = 6) were pair-fed the control diets to match the intake of the ZD rats. Two fluid bottles with deionized water were attached to each cage for the entire experiment with the exception of the 48 h preference test, in which 300 mM NaCl was provided from days 6 to 8. Zinc was limited for 10 days to reduce the effects of differences in salt intake in the preference test between the two groups. For the zinc recovery experiment, the ZR (n = 9) and ZRPF (n = 6) groups were subjected to the same conditions as above. Briefly, after 1 week of adaptation, ZR rats were fed the zinc-deficient diets ad libitum, and ZRPF rats were pair-fed the control diets for 10 days. After that, the rats in both the ZR and ZRPF groups were fed the fixed amount (13 g) of the control diets for the 6 day zinc recovery period to avoid any differences in food intake between the two groups that would be caused by pair-feeding because the previous report showed rapidly increased food intake following the initiation of the zinc-sufficient diets after zinc deficiency [1]. The diet amounts were restricted to the average consumption of the ZR group on the last day of the zinc-deficient period. The 48 h two-bottle preference tests for 300 mM NaCl were performed from days 6 to 8 during the deficient period and from days 14 to 16 during the recovery period. The analysis removed one rat from the ZRPF group showing more than a 0.5 of preference ratio to the 300 mM NaCl solution and three rats from the ZR group showing less than 0.5 preference ratios as assessed by a preference test that was conducted during days 6 to 8. At the end of each experiment, the rats were deeply anesthetized with pentobarbital sodium. Blood samples were collected from the carotid arteries and stored at -80 Â°C. The brains were quickly removed from the bodies after decapitation, and the diencephalons were separated by forceps on ice. The diencephalons were washed in ice-cold phosphate-buffered saline (PBS), treated with RNAlater (Invitrogen, Carlsbad, CA, USA), and stored at -20 Â°C. The serum zinc concentrations were analyzed with an ICP-AES (SPS 1200 VR, Seiko Instruments, Chiba, Japan). The Animal Care Committee of the University of Tokyo approved all animal experiments. Four average rats from each group were selected based on body weights, plasma zinc concentrations, and salt preferences.

Dataset Information

Identification of a Novel Angiogenesis and Tumor Suppressor Gene Rab25 in Esophageal Squamous Cell Carcinoma

Publications

Rab25 is a tumor suppressor gene with antiangiogenic and anti-invasive activities in esophageal squamous cell carcinoma.

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