Dataset Information

Comprehensive Characterization of the RNA Editomes in Cancer Development and Progression.

ABSTRACT: RNA editing is a post-transcriptional event that leads to transcriptome diversity and has been shown to play important roles in tumorigenesis. However, dynamical changes and the functional significance of editing events during different cancer stages have not yet been characterized systematically. In this paper, we describe a comprehensive study of the RNA editome of four samples from different cancer stages for the same patient based on analysis of both whole-genome and transcriptome sequencing data. We identified 35,225 and 33,784 RNA editing events for poly(A)+ and poly(A)- RNA sequencing data respectively in all four samples and show that 93 and 90% correspond to cancer stage-specific editing events. We also found that half of editing sites in 3' UTR of coding genes were microRNA targets and most of the sites in the coding regions could lead to non-synonymous amino acid changes. Functional analysis of genes which suffered damaging non-synonymous editing events in each cancer stage show the gradual expansion of cancer related pathways accompanied by an increasing malignant grade of the samples. Our study, for the first time to our knowledge, comprehensively profiled and compared the editomes across the different cancer stages and revealed the functional impacts of RNA editing events during cancer development and progression.

SUBMITTER: Luo H

PROVIDER: S-EPMC5776088 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Comprehensive Characterization of the RNA Editomes in Cancer Development and Progression.

Luo Haitao H Fang Shuangsang S Sun Liang L Liu Zhiyong Z Zhao Yi Y

Frontiers in genetics 20180117

RNA editing is a post-transcriptional event that leads to transcriptome diversity and has been shown to play important roles in tumorigenesis. However, dynamical changes and the functional significance of editing events during different cancer stages have not yet been characterized systematically. In this paper, we describe a comprehensive study of the RNA editome of four samples from different cancer stages for the same patient based on analysis of both whole-genome and transcriptome sequencing ...[more]

PMID: 29387082

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Project description:Bladder cancer (BC) is one of the most common malignant tumors in males globally. Its progression imposes a heavy burden on patients; however, the expression profile of circular (circ)RNAs in BC progression remains unclear. This study explored changes in circRNA expression during BC progression by sequencing different grade BC samples and normal controls to reveal the circRNA expression profiles of different BC grades. Gene Ontology (GO) and Kyoto Encyclopedia of Gens and Genomes (KEGG) pathway analyses, and protein‑protein interaction network construction were used to predict pathways that the differentially expressed circRNAs may participate in. circRNA expression levels were detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and dual‑luciferase reporter assays were used to investigate the interactions between circRNA and microRNA (miR). Cell Counting Kit‑8 and Transwell assays were also performed to detect cell proliferation, migration, and invasion. In total, 244 circRNAs were found to be differentially expressed in high‑grade BC compared to low‑grade BC, whilst 316 dysregulated circRNAs were detected in high‑grade BC compared with normal urothelium. Furthermore, 42 circRNAs overlapped between the two groups, seven of which were randomly selected and detected by RT‑qPCR to validate the sequencing results. GO analysis and KEGG pathway analyses revealed that the differentially expressed circRNAs may participate in BC via 'GTPase activity regulation', 'cell junction', and 'focal adhesion' pathways. Of note, we proposed that a novel circRNA in BC progression, hsa_circ_0137606, could suppress BC proliferation and metastasis by sponging miR‑1231. Through bioinformatics analysis, we predicted that PH domain and leucine rich repeat protein phosphatase 2 could be a target of the hsa_circ_0137606/miR‑1231 axis in BC progression. Using high‑throughput sequencing, this study revealed the circRNA expression profiles of different grades of BC and proposed that the novel circRNA, hsa_circ_0137606, suppresses BC proliferation and metastasis by sponging miR‑1231. Our findings may provide novel insight into potential therapeutic targets for treating BC.

Dataset Information

Comprehensive Characterization of the RNA Editomes in Cancer Development and Progression.

Publications

Comprehensive Characterization of the RNA Editomes in Cancer Development and Progression.

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