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AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer
Kunitoshi Shigeyasu, … , Leilei Chen, Ajay Goel
Kunitoshi Shigeyasu, … , Leilei Chen, Ajay Goel
Published June 21, 2018
Citation Information: JCI Insight. 2018;3(12):e99976. https://doi.org/10.1172/jci.insight.99976.
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Research Article Gastroenterology Oncology

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

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Abstract

Adenosine-to-inosine (A-to-I) RNA editing, a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family, is a recently discovered epigenetic modification dysregulated in human cancers. However, the clinical significance and the functional role of RNA editing in colorectal cancer (CRC) remain unclear. We have systematically and comprehensively investigated the significance of the expression status of ADAR1 and of the RNA editing levels of antizyme inhibitor 1 (AZIN1), one of the most frequently edited genes in cancers, in 392 colorectal tissues from multiple independent CRC patient cohorts. Both ADAR1 expression and AZIN1 RNA editing levels were significantly elevated in CRC tissues when compared with corresponding normal mucosa. High levels of AZIN1 RNA editing emerged as a prognostic factor for overall survival and disease-free survival and were an independent risk factor for lymph node and distant metastasis. Furthermore, elevated AZIN1 editing identified high-risk stage II CRC patients. Mechanistically, edited AZIN1 enhances stemness and appears to drive the metastatic processes. We have demonstrated that edited AZIN1 functions as an oncogene and a potential therapeutic target in CRC. Moreover, AZIN1 RNA editing status could be used as a clinically relevant prognostic indicator in CRC patients.

Authors

Kunitoshi Shigeyasu, Yoshinaga Okugawa, Shusuke Toden, Jinsei Miyoshi, Yuji Toiyama, Takeshi Nagasaka, Naoki Takahashi, Masato Kusunoki, Tetsuji Takayama, Yasuhide Yamada, Toshiyoshi Fujiwara, Leilei Chen, Ajay Goel

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Figure 4

AZIN1 RNA editing promotes stemness in CRC cells.

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AZIN1 RNA editing promotes stemness in CRC cells.
(A) Spheroids establi...
(A) Spheroids established from HT29 and HCT116 cells (scale bar: 100 μm; original magnification, ×100). (B) OCT4 and SOX2 RNA expression levels in parental cells and spheroids derived from HT29 or HCT116 cell lines (n = 3) (Wilcoxon’s rank-sum test). (C) AZIN1 RNA editing levels and ADAR1 expression levels in parental cells and spheroids derived from HT29 and HCT116 cell lines (n = 3) (Wilcoxon’s rank-sum test). (D) Comparison of spheroid formation by HT29 and HCT116 cells overexpressing wild-type or edited AZIN1 with cells transfected with empty vector (n = 12) (Steel test) (scale bar: 250 μm; original magnification, ×40). (E) OCT4 and SOX2 RNA expression levels in spheroids derived from either wild-type or edited AZIN1 overexpressing HT29 and HCT116 cells (n = 3) (Wilcoxon’s rank-sum test). (F) CD44v6 protein expression in HT29 and HCT116 cells transfected with empty, wild-type, or edited AZIN1-containing plasmids. *P < 0.05, **P < 0.01, ***P < 0.001.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

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