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

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
JournalJCI Insight
Volume3
Issue number12
DOIs
Publication statusPublished - Jun 21 2018
Externally publishedYes

Keywords

  • Colorectal cancer
  • Epigenetics
  • Gastroenterology
  • Oncology
  • RNA processing

ASJC Scopus subject areas

  • Medicine(all)

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    Shigeyasu, K., Okugawa, Y., Toden, S., Miyoshi, J., Toiyama, Y., Nagasaka, T., Takahashi, N., Kusunoki, M., Takayama, T., Yamada, Y., Fujiwara, T., Chen, L., & Goel, A. (2018). AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer. JCI Insight, 3(12). https://doi.org/10.1172/jci.insight.99976