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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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Quantitative polymerase chain reaction analysis of tandem 3′ UTR genes in nine patients with esophageal cancer. (A) SORBS1, (B) SMAD4, (C) RBL2, (D) CDKN1B, (E) CCND1 and (F) HDAC2. cUTR/eUTR represents the expression ratio of of the shortened region to the lengthened region. *P<0.05. UTR, untranslated region; cUTR, constitutive UTR; eUTR, extended UTR; SORBS1, sorbin and SH3 domain containing 1; SMAD4, SMAD family homolog 4; RBL2, retinoblastoma-like 2; CDKN1B; cyclin-dependent kinase inhibitor 1B; CCND1, cyclin D1; HDAC2, histone deacetylase 2.
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f4-mmr-09-05-1597: Quantitative polymerase chain reaction analysis of tandem 3′ UTR genes in nine patients with esophageal cancer. (A) SORBS1, (B) SMAD4, (C) RBL2, (D) CDKN1B, (E) CCND1 and (F) HDAC2. cUTR/eUTR represents the expression ratio of of the shortened region to the lengthened region. *P<0.05. UTR, untranslated region; cUTR, constitutive UTR; eUTR, extended UTR; SORBS1, sorbin and SH3 domain containing 1; SMAD4, SMAD family homolog 4; RBL2, retinoblastoma-like 2; CDKN1B; cyclin-dependent kinase inhibitor 1B; CCND1, cyclin D1; HDAC2, histone deacetylase 2.

Mentions: Seven genes with significantly shortened tandem 3′ UTRs were selected for qPCR analysis. Six of the seven genes were successfully verified in more than four patients, including the patient used for SAPAS sequencing (Fig. 4). The seven genes were as follows: Sorbin and SH3 domain containing 1 (SORBS1), SMAD family member 4 (SMAD4), retinoblastoma-like 2 (RBL2), cyclin-dependent kinase inhibitor 1B (CDKN1B), cyclin D1 (CCND1) and histone deacetylase 2 (HDAC2). SORBS1 was enriched in adherens junctions, SMAD4 was enriched in adherens junctions and the cell cycle, RBL2 and CDKN1B were enriched in the cell cycle and HDAC2 was enriched in the notch signaling pathway and the cell cycle.


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)

Quantitative polymerase chain reaction analysis of tandem 3′ UTR genes in nine patients with esophageal cancer. (A) SORBS1, (B) SMAD4, (C) RBL2, (D) CDKN1B, (E) CCND1 and (F) HDAC2. cUTR/eUTR represents the expression ratio of of the shortened region to the lengthened region. *P<0.05. UTR, untranslated region; cUTR, constitutive UTR; eUTR, extended UTR; SORBS1, sorbin and SH3 domain containing 1; SMAD4, SMAD family homolog 4; RBL2, retinoblastoma-like 2; CDKN1B; cyclin-dependent kinase inhibitor 1B; CCND1, cyclin D1; HDAC2, histone deacetylase 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-mmr-09-05-1597: Quantitative polymerase chain reaction analysis of tandem 3′ UTR genes in nine patients with esophageal cancer. (A) SORBS1, (B) SMAD4, (C) RBL2, (D) CDKN1B, (E) CCND1 and (F) HDAC2. cUTR/eUTR represents the expression ratio of of the shortened region to the lengthened region. *P<0.05. UTR, untranslated region; cUTR, constitutive UTR; eUTR, extended UTR; SORBS1, sorbin and SH3 domain containing 1; SMAD4, SMAD family homolog 4; RBL2, retinoblastoma-like 2; CDKN1B; cyclin-dependent kinase inhibitor 1B; CCND1, cyclin D1; HDAC2, histone deacetylase 2.
Mentions: Seven genes with significantly shortened tandem 3′ UTRs were selected for qPCR analysis. Six of the seven genes were successfully verified in more than four patients, including the patient used for SAPAS sequencing (Fig. 4). The seven genes were as follows: Sorbin and SH3 domain containing 1 (SORBS1), SMAD family member 4 (SMAD4), retinoblastoma-like 2 (RBL2), cyclin-dependent kinase inhibitor 1B (CDKN1B), cyclin D1 (CCND1) and histone deacetylase 2 (HDAC2). SORBS1 was enriched in adherens junctions, SMAD4 was enriched in adherens junctions and the cell cycle, RBL2 and CDKN1B were enriched in the cell cycle and HDAC2 was enriched in the notch signaling pathway and the cell cycle.

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