Identification of Diverse Adenosine-to-Inosine RNA Editing Subtypes in Colorectal Cancer.
OBJECTIVE
RNA editing generates protein diversity by altering RNA sequences in coding regions without changing the overall DNA sequence. Adenosine-to-inosine (A-to-I) RNA editing events have recently been reported in some types of cancer, but they are rare in human colorectal cancer (CRC). Therefore, this study was conducted to identify diverse RNA editing in CRC.


METHODS
We compared transcriptome data of 39 CRC samples and paired adjacent tissues from The Cancer Genome Atlas database to identify RNA editing patterns in CRC, focusing on canonical A-to-I RNA edits in coding sequence regions. We investigated nonsynonymous RNA editing patterns by comparing tumor and normal tissue transcriptome data.


RESULTS
The number of RNA edits varied from 12 to 42 per sample. We also observed that hypoand hyper-RNA editing patterns were distinguishable within the samples. We found 10 recurrent nonsynonymous RNA editing candidates in nine genes (PDLIM, NEIL1, SRP9, GLI1, APMAP, IGFBP7, ZNF358, COPA, and ZNF587B) and validated some by Sanger sequencing and the inosine chemical erasing assay. We further showed that editing at these positions was performed by the adenosine deaminase acting on RNA 1 enzyme. Most of these genes are hypoedited in CRC, but editing of GLI1 was increased in cancer tissues compared with normal tissues.


CONCLUSIONS
Our results show that nonsynonymous RNA editing patterns can be used to identify CRC patients and could serve as novel biomarkers for CRC.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea.
Si-Hyun
SH
Lee
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Hwang-Phill
HP
Kim
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Jun-Kyu
JK
Kang
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Sang-Hyun
SH
Song
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Sae-Won
SW
Han
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Tae-You
TY
Kim
D000241:Adenosine / Q000235:genetics*; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D007288:Inosine / Q000235:genetics*; D017393:RNA Editing; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D059467:Transcriptome
D014408:Biomarkers, Tumor; D007288:Inosine; D000241:Adenosine
Adenosine deaminase; Colorectal neoplasms; GLI family zinc finger 1; RNA editing; Transcriptome sequencing