Altered expression and functional roles of the transcribed ultraconserved regions (T-UCRs), as genomic sequences with 100% conservation between the genomes of human, mouse, and rat, in the pathophysiology of neoplasms has already been investigated. Nevertheless, the relevance of the functions for T-UCRs in gastric cancer (GC) is still the subject of inquiry. In the current study, we first used a genome-wide profiling approach to analyze the expression of T-UCRs in GC patients. Then, we constructed a threecomponent regulatory network and investigated potential diagnostic and prognostic values of the T-UCRs. The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset was used as a resource for the RNA-sequencing data. FeatureCounts was utilized to quantify the number of reads mapped to each T-UCR. Differential expression analysis was then conducted using DESeq2. In the following, interactions between T-UCRs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were combined into a three-component network. Enrichment analyses were performed and a protein-protein interaction (PPI) network was constructed. The R Survival package was utilized to identify survival-related significantly differentially expressed T-UCRs (DET-UCRs). Using an in-house cohort of GC tissues, expression of two DET-UCRs was furthermore experimentally verified. Our results showed that several T-UCRs were dysregulated in TCGA-STAD tumoral samples compared to nontumoral counterparts. The three-component network was constructed which composed of DET-UCRs, miRNAs, and mRNAs nodes. Functional enrichment and PPI network analyses revealed important enriched signaling pathways and gene ontologies such as "pathway in cancer" and regulation of cell proliferation and apoptosis. Five T-UCRs were significantly correlated with the overall survival of GC patients. While no expression of uc.232 was observed in our in-house cohort of GC tissues, uc.343 showed an increased expression, although not statistically significant, in gastric tumoral tissues. The constructed three-component regulatory network of

Background: Celiac disease (CeD) is an autoimmune enteropathy triggered by dietary gluten. Almost 90% of CeD patients have HLA-DQ2 or -DQ8 haplotypes. As a high proportion of first-degree relatives (FDRs) of CeD patients have the same haplotype, it is assumed that they are at a higher risk of disease development than the general population. Nevertheless, the prevalence of CeD among FDRs is considerably low (7.5%). Methods: In order to figure out this discrepancy, a microarray dataset of intestinal mucosal biopsies from CeD, FDR, and control groups was reanalyzed, and gene co-expression network using WGCNA was constructed. The differentially expressed genes in the opposite modules from the consensus analysis were applied for functional enrichment analysis. Results: WGCNA analysis identified 10 consensus modules in both CeD and FDR groups, including 5 modules with opposite correlation. Among the genes of opposing modules, 159 of them were identified as commonly differentially expressed genes with an adjusted p-value< 0.05 between FDR and CeD groups. Functional enrichment analysis revealed the significant contributions of these genes in host energy metabolism, programmed cell death, antigen cross presentation, and actin folding. In a deep view to the relation of actin folding to celiac disease occurrence, it was found that misfolding of actin and presentation of anti-actin antibodies occur in CeD patients. The current study reports that this pathway is oppositely regulated in FDR group and this might be a trigger for celiac manifestation. Conclusions: The consensus signaling pathways with opposing expression patterns identified in this study give us a clue about the gene circuits that are dysregulated in celiac patients. Considering the prominent relation of actin folding to disease occurrence and its opposite manner in celiac patients and healthy individuals, it is proposed that targeting CCT/TriC chaperonin family might result in a reduction of misfolded actin and the production of autoantibodies.

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Although altered expression and functional roles of the transcribed ultraconserved regions (T-UCRs) in the pathophysiology of neoplasms has already been investigated, relevance of the functions for T-UCRs in gastric cancer (GC) is still the subject of inquiry. In the current study, The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset was used as a resource for the RNA-sequencing data. Differential expression analysis was conducted using DESeq2. Interactions between T-UCRs, miRNAs, and mRNAs were combined into a three-component network. The Survival package was utilized to identify survival-related differentially-expressed T-UCRs (DET-UCRs). Using an in-house cohort of GC tissues, expression of two DET-UCRs was experimentally verified. Thirty-four T-UCRs were dysregulated in TCGA-STAD tumoral samples compared to non-tumoral counterparts. The network was composed of 34 DET-UCRs, 275 miRNAs and 796 mRNAs nodes. Five T-UCRs were significantly correlated with the overall survival. While no expression of uc.232 was observed in our in-house cohort of GC tissues, uc.343 showed an increased expression in gastric tumoral tissues. The constructed three-component regulatory network of T-UCRs in GC presents a comprehensive understanding of the underlying gene expression regulation processes involved in tumor development and can serve as a basis to investigate potential prognostic biomarkers and therapeutic targets.

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