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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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Characteristics of the poly(A) sites of one patient with squamous cell carcinoma. (A) Distribution of the number of poly(A) sites per gene. (B) Genomic location of the poly(A) sites in all genes. UTR, untranslated region; Inter, intergenic; Non, noncoding gene; <1 knt, <1 knt downstream; Tian, Tian polyA_DB; TES, polyA sites that are located within 24 nt downstream of 3′ transcript end of UCSC canonical genes; CDS, conding DNA sequence.
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f2-mmr-09-05-1597: Characteristics of the poly(A) sites of one patient with squamous cell carcinoma. (A) Distribution of the number of poly(A) sites per gene. (B) Genomic location of the poly(A) sites in all genes. UTR, untranslated region; Inter, intergenic; Non, noncoding gene; <1 knt, <1 knt downstream; Tian, Tian polyA_DB; TES, polyA sites that are located within 24 nt downstream of 3′ transcript end of UCSC canonical genes; CDS, conding DNA sequence.

Mentions: The APA sites of 15,186 and 14,486 genes (Table II) were annotated in the normal and cancerous tissue samples, respectively. Subsequent to filtering the polyA sites supported by solely one read, 14,597 and 13,658 genes with polyA sites were obtained for the normal and cancerous tissue, respectively. ~88.6% of the reads were mapped to the region within 24 nt of the known polyA sites. Furthermore, 2.1 and 0.7% of the reads mapped to the 3′ UTR region of UCSC (http://genome.ucsc.edu/) canonical gene and 1 kb downstream of the end of the genes, respectively (Fig. 1). In the normal tissue, 10,850 genes (71.4%) were annotated with more than one polyA site and 8,072 genes (54.2%) were annotated with more than two polyA sites (Fig. 2A). The reads distribution for the number of polyA sites within 10 is shown in Fig. 1. Among the 75,257 annotated polyA sites in the normal tissue, 24.3% of the sites were recorded in the polyA_DB2 database (28). This suggests that a greater number of novel polyA sites are detected in the genome using the SAPAS method, particularly those in lowly expressed mRNA (Fig. 2B).


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)

Characteristics of the poly(A) sites of one patient with squamous cell carcinoma. (A) Distribution of the number of poly(A) sites per gene. (B) Genomic location of the poly(A) sites in all genes. UTR, untranslated region; Inter, intergenic; Non, noncoding gene; <1 knt, <1 knt downstream; Tian, Tian polyA_DB; TES, polyA sites that are located within 24 nt downstream of 3′ transcript end of UCSC canonical genes; CDS, conding DNA sequence.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-09-05-1597: Characteristics of the poly(A) sites of one patient with squamous cell carcinoma. (A) Distribution of the number of poly(A) sites per gene. (B) Genomic location of the poly(A) sites in all genes. UTR, untranslated region; Inter, intergenic; Non, noncoding gene; <1 knt, <1 knt downstream; Tian, Tian polyA_DB; TES, polyA sites that are located within 24 nt downstream of 3′ transcript end of UCSC canonical genes; CDS, conding DNA sequence.
Mentions: The APA sites of 15,186 and 14,486 genes (Table II) were annotated in the normal and cancerous tissue samples, respectively. Subsequent to filtering the polyA sites supported by solely one read, 14,597 and 13,658 genes with polyA sites were obtained for the normal and cancerous tissue, respectively. ~88.6% of the reads were mapped to the region within 24 nt of the known polyA sites. Furthermore, 2.1 and 0.7% of the reads mapped to the 3′ UTR region of UCSC (http://genome.ucsc.edu/) canonical gene and 1 kb downstream of the end of the genes, respectively (Fig. 1). In the normal tissue, 10,850 genes (71.4%) were annotated with more than one polyA site and 8,072 genes (54.2%) were annotated with more than two polyA sites (Fig. 2A). The reads distribution for the number of polyA sites within 10 is shown in Fig. 1. Among the 75,257 annotated polyA sites in the normal tissue, 24.3% of the sites were recorded in the polyA_DB2 database (28). This suggests that a greater number of novel polyA sites are detected in the genome using the SAPAS method, particularly those in lowly expressed mRNA (Fig. 2B).

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