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

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.

Profiling of alternative polyadenylation sites in luminal B breast cancer using the SAPAS method

“…With UCSC Known Genes ( 19 ) and polyA_DB2 ( 22 ), all the poly(A) sites were annotated as known and novel sites. The annotation procedure was the same as in the study by Sun et al ( 23 ). On the basis of their locations on the genome, all the novel sites were classified as ≤1 knt downstream, 3′UTRs, coding DNA sequences, intergenic sequences, introns and non-coding genes.…”

“…Briefly, the 3′UTR length for each tandem poly(A) site was calculated. A column chain table was then generated as in the study by Sun et al ( 23 ). Pearson’s correlation co-efficient r, which was in short for tandem APA sites switch index (TSI), was then calculated.…”

Dynamic Variations of 3′UTR Length Reprogram the mRNA Regulatory Landscape

“…While long 3′UTRs have been mostly detected in quiescent stem cells, differentiated cells, or early in development, shortened 3′UTRs have been mostly described in quickly cycling cells such as proliferative stem/progenitor cells or tumour cells [ 85 , 86 , 87 ]. Thus, shortened 3′UTRs have been reported in proliferation-related transcripts in triple negative breast cancers [ 88 ], non-small cell lung cancer [ 89 ], glioblastoma [ 90 ], esophageal carcinoma [ 91 ], multiple myeloma [ 92 ], colorectal cancer [ 93 ] cardiac hypertrophy [ 94 ], etc. Furthermore, aberrant APA dynamics has been also described in acute myeloid leukemia and mature erythroid cells [ 95 ], neurological disorders [ 96 ], hypertrophic heart [ 97 ], heart failure [ 98 ] as well as in arsenic stress [ 99 ], while neurons were shown to express 3′UTRs longer than other brain cells [ 100 ].…”

Roles of Major RNA Adenosine Modifications in Head and Neck Squamous Cell Carcinoma

“…Meanwhile, 195 genes were also identified in NPC and their tandem 3′-UTR lengths were significantly different between NPC and the control group ( Xu et al, 2018 ). In esophageal squamous cell carcinomas, 903 genes related to adhesion junctions and the cell cycle shortened the 3′-UTR, and the distal PolyA site was used by 917 genes ( Sun et al, 2014 ). This difference may be caused by APA-mediated gene expression regulation.…”