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Pilot genome-wide study of tandem 3' UTRs in esophageal cancer using high-throughput sequencing.

Sun M, Ju H, Zhou Z, Zhu R - Mol Med Rep (2014)

Bottom Line: The genes with shortened 3' UTRs were primarily associated with adherens junctions and the cell cycle.Four differentially expressed genes were also found, among which three genes were observed to be upregulated in cancerous tissue and involved in the positive regulation of cell motion, migration and locomotion.One gene was found to be downregulated in cancerous tissue, and associated with oxidative phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, Jiangsu 224001, P.R. China.

ABSTRACT
Regulatory regions within the 3' untranslated region (UTR) influence polyadenylation (polyA), translation efficiency, localization and stability of mRNA. Alternative polyA (APA) has been considered to have a key role in gene regulation since 2008. Esophageal carcinoma is the eighth most common type of cancer worldwide. The association between polyA and disease highlights the requirement for comprehensive characterization of genome-wide polyA profiles. In the present study, global polyA profiles were established using the sequencing APA sites (SAPAS) method in order to elucidate the interrelation between 3' UTR length and the development of esophageal cancer. PolyA profiles were analyzed in squamous cell carcinoma, with ~903 genes identified to have shortened 3' UTRs and 917 genes identified to use distal polyA sites. The genes with shortened 3' UTRs were primarily associated with adherens junctions and the cell cycle. Four differentially expressed genes were also found, among which three genes were observed to be upregulated in cancerous tissue and involved in the positive regulation of cell motion, migration and locomotion. One gene was found to be downregulated in cancerous tissue, and associated with oxidative phosphorylation. These findings suggest that esophagitis may have a key role in the development of esophageal carcinoma. Furthermore, the genes with tandem 3' UTRs and differential expression identified in the present study may have the potential to be used as biomarkers for the diagnosis and prognosis of esophageal cancer.

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Related in: MedlinePlus

APA site switching and gene expression in normal and cancerous tissue. TSI values are plotted against the Log2 of the expression level of genes from the cancerous tissues relative to normal tissues. Larger TSI values indicate that longer tandem UTRs are present in carcinoma tissues. Genes with significant switching to longer (blue) or shorter (red) tandem UTRs in cancerous tissues are colored (false discovery rate<0.01). Nor, normal tissue; Exp, expression; TSI, tandem APA site switch index; UTR, untranslated region. APA, alternative polyadenylation.
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f3-mmr-09-05-1597: APA site switching and gene expression in normal and cancerous tissue. TSI values are plotted against the Log2 of the expression level of genes from the cancerous tissues relative to normal tissues. Larger TSI values indicate that longer tandem UTRs are present in carcinoma tissues. Genes with significant switching to longer (blue) or shorter (red) tandem UTRs in cancerous tissues are colored (false discovery rate<0.01). Nor, normal tissue; Exp, expression; TSI, tandem APA site switch index; UTR, untranslated region. APA, alternative polyadenylation.

Mentions: A total of 1,820 genes was identified to show a significant difference in tandem 3′ UTR length (FDR<0.01). Among these genes, 50.4% (903) had a negative TSI, suggesting that the number of genes with shortened 3′ UTRs in the cancerous tissue was approximately equal to the number of those with lengthened 3′ UTRs (Fig. 3). The shortened genes in the cancerous tissue were enriched in 119 gene ontology (GO) terms primarily associated with protein transport and the establishment of protein localization (FDR<0.01; data not shown). The cell components encoded by these GO term-enriched genes were associated with membrane-enclosed lumens and the internal side of the plasma membrane (FDR<0.01). All genes were enriched in the following 11 pathways: Chronic myeloid leukemia, adherens junction, SNARE interactions in vesicular transport, cyanoamino acid metabolism, notch signaling, T-cell receptor signaling, cell cycle, spliceosome, biosynthesis of unsaturated fatty acids, Fcγ receptor-mediated phagocytosis and nitrogen metabolism (Table III). The lengthened genes in cancerous tissues were enriched in 141 GO terms, which were associated with one biological process: Intracellular transport (FDR<0.01; data not shown). All genes were enriched in the following six pathways: Lysosome, nucleotide excision repair, wingless-type MMTV integration site family signaling, ubiquitin mediated proteolysis, porphyrin and chlorophyll metabolism and spliceosomes (Table IV).


Pilot genome-wide study of tandem 3' UTRs in esophageal cancer using high-throughput sequencing.

Sun M, Ju H, Zhou Z, Zhu R - Mol Med Rep (2014)

APA site switching and gene expression in normal and cancerous tissue. TSI values are plotted against the Log2 of the expression level of genes from the cancerous tissues relative to normal tissues. Larger TSI values indicate that longer tandem UTRs are present in carcinoma tissues. Genes with significant switching to longer (blue) or shorter (red) tandem UTRs in cancerous tissues are colored (false discovery rate<0.01). Nor, normal tissue; Exp, expression; TSI, tandem APA site switch index; UTR, untranslated region. APA, alternative polyadenylation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4020480&req=5

f3-mmr-09-05-1597: APA site switching and gene expression in normal and cancerous tissue. TSI values are plotted against the Log2 of the expression level of genes from the cancerous tissues relative to normal tissues. Larger TSI values indicate that longer tandem UTRs are present in carcinoma tissues. Genes with significant switching to longer (blue) or shorter (red) tandem UTRs in cancerous tissues are colored (false discovery rate<0.01). Nor, normal tissue; Exp, expression; TSI, tandem APA site switch index; UTR, untranslated region. APA, alternative polyadenylation.
Mentions: A total of 1,820 genes was identified to show a significant difference in tandem 3′ UTR length (FDR<0.01). Among these genes, 50.4% (903) had a negative TSI, suggesting that the number of genes with shortened 3′ UTRs in the cancerous tissue was approximately equal to the number of those with lengthened 3′ UTRs (Fig. 3). The shortened genes in the cancerous tissue were enriched in 119 gene ontology (GO) terms primarily associated with protein transport and the establishment of protein localization (FDR<0.01; data not shown). The cell components encoded by these GO term-enriched genes were associated with membrane-enclosed lumens and the internal side of the plasma membrane (FDR<0.01). All genes were enriched in the following 11 pathways: Chronic myeloid leukemia, adherens junction, SNARE interactions in vesicular transport, cyanoamino acid metabolism, notch signaling, T-cell receptor signaling, cell cycle, spliceosome, biosynthesis of unsaturated fatty acids, Fcγ receptor-mediated phagocytosis and nitrogen metabolism (Table III). The lengthened genes in cancerous tissues were enriched in 141 GO terms, which were associated with one biological process: Intracellular transport (FDR<0.01; data not shown). All genes were enriched in the following six pathways: Lysosome, nucleotide excision repair, wingless-type MMTV integration site family signaling, ubiquitin mediated proteolysis, porphyrin and chlorophyll metabolism and spliceosomes (Table IV).

Bottom Line: The genes with shortened 3' UTRs were primarily associated with adherens junctions and the cell cycle.Four differentially expressed genes were also found, among which three genes were observed to be upregulated in cancerous tissue and involved in the positive regulation of cell motion, migration and locomotion.One gene was found to be downregulated in cancerous tissue, and associated with oxidative phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, Jiangsu 224001, P.R. China.

ABSTRACT
Regulatory regions within the 3' untranslated region (UTR) influence polyadenylation (polyA), translation efficiency, localization and stability of mRNA. Alternative polyA (APA) has been considered to have a key role in gene regulation since 2008. Esophageal carcinoma is the eighth most common type of cancer worldwide. The association between polyA and disease highlights the requirement for comprehensive characterization of genome-wide polyA profiles. In the present study, global polyA profiles were established using the sequencing APA sites (SAPAS) method in order to elucidate the interrelation between 3' UTR length and the development of esophageal cancer. PolyA profiles were analyzed in squamous cell carcinoma, with ~903 genes identified to have shortened 3' UTRs and 917 genes identified to use distal polyA sites. The genes with shortened 3' UTRs were primarily associated with adherens junctions and the cell cycle. Four differentially expressed genes were also found, among which three genes were observed to be upregulated in cancerous tissue and involved in the positive regulation of cell motion, migration and locomotion. One gene was found to be downregulated in cancerous tissue, and associated with oxidative phosphorylation. These findings suggest that esophagitis may have a key role in the development of esophageal carcinoma. Furthermore, the genes with tandem 3' UTRs and differential expression identified in the present study may have the potential to be used as biomarkers for the diagnosis and prognosis of esophageal cancer.

Show MeSH
Related in: MedlinePlus