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Updated: Aug 7, 2025
A Nonsequencing Approach for the Rapid Detection of RNA Editing
Published on: April 21, 2022
Genome-wide identification of A-to-I RNA editing events provides the functional implications in PDAC
Yue Mei1,2, Dong Liang1,2, Bin Ai1,2
1Department of Precision Medicine, Translational Medicine Research Center, Naval Medical University, Shanghai, China.
Introduction:
RNA editing, a wide-acknowledged post-transcriptional mechanism, has been reported to be involved in the occurrence and development of cancer, especially the abnormal alteration of adenosine to inosine. However, fewer studies focus on pancreaticcancer. Therefore, we aimed to explore the possible linkages between altered RNA editing events and the development of PDAC.
Method:
We characterized the global A-to-I RNA editing spectrum from RNA and matched whole-genome sequencing data of 41 primary PDAC and adjacent normal tissues. The following analyses were performed: different editing level and RNA expression analysis,pathway analysis, motif analysis, RNA secondary structure analysis, alternative splicing events analysis, and survival analysis.The RNA editing of single-cell RNA public sequencing data was also characterized.
Result:
A large number of adaptive RNA editing events with significant differences in editing levels were identified, which are mainly regulated by ADAR1. Moreover, RNA editing in tumors has a higher editing level and more abundant editing sites in general. 140genes were screened out since they were identified with significantly different RNA editing events and were significantly different in expression level between tumor and matched normal samples. Further analysis showed a preference that in the tumor-specific group, they are mainly enriched in cancer-related signal pathways, while in the normal tissue-specific group, they are mainly enriched in pancreatic secretion. At the same time, we also found positively selected differentially edited sites in a series of cancer immune genes, including EGF, IGF1R, and PIK3CD. RNA editing might participate in pathogenisis of PDAC through regulating the alternative splicing and RNA secondary structure of important genesto further regulate gene expression and protein synthesis, including RAB27B and CERS4. Furthermore, single cell sequencing results showed that type2 ductal cells contributed the most to RNA editing events in tumors.
Conclusion:
RNA editing is an epigenetic mechanism involved in the occurrence and development of pancreatic cancer, which has the potential to diagnose of PDAC and is closely related to the prognosis.
Insights
RNA editing, particularly adenosine-to-inosine alterations, plays a role in pancreatic ductal adenocarcinoma (PDAC) development. These epigenetic changes impact gene expression and offer potential diagnostic and prognostic insights for PDAC.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- RNA editing is a post-transcriptional mechanism implicated in cancer development.
- Adenosine-to-inosine (A-to-I) RNA editing is a common type, but its role in pancreatic ductal adenocarcinoma (PDAC) is understudied.
Purpose of the Study:
- To investigate the association between altered RNA editing events and the development of PDAC.
- To characterize the global RNA editing spectrum in PDAC tissues.
Main Methods:
- Genome-wide RNA and whole-genome sequencing of 41 primary PDAC and adjacent normal tissues.
- Analysis of editing levels, RNA expression, pathways, motifs, RNA secondary structures, and alternative splicing.
- Characterization of RNA editing in single-cell RNA sequencing data.
Main Results:
- Identified numerous adaptive RNA editing events, primarily regulated by ADAR1, with higher levels and more sites in tumors.
- Screened 140 genes with differential editing and expression, enriched in cancer pathways (tumor) or pancreatic secretion (normal).
- Discovered differentially edited sites in cancer immune genes (e.g., EGF, IGF1R) and identified RNA editing's role in regulating alternative splicing and gene expression (e.g., RAB27B, CERS4).
Conclusions:
- RNA editing is an epigenetic mechanism crucial for PDAC occurrence and progression.
- Altered RNA editing events in PDAC are linked to prognosis and hold diagnostic potential.
