1. Academic Validation
  2. A novel mechanism for A-to-I RNA-edited AZIN1 in promoting tumor angiogenesis in colorectal cancer

A novel mechanism for A-to-I RNA-edited AZIN1 in promoting tumor angiogenesis in colorectal cancer

  • Cell Death Dis. 2022 Apr 2;13(4):294. doi: 10.1038/s41419-022-04734-8.
Yan Wei  # 1 Haowan Zhang  # 1 Qiaohui Feng  # 2 Shumin Wang 1 Youcheng Shao 1 Jie Wu 1 Ge Jin 1 Weiwei Lin 1 Xinxin Peng 3 Xiaoyan Xu 4
Affiliations

Affiliations

  • 1 Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, 110122, Liaoning, PR China.
  • 2 Innovation Institute, China Medical University, Shenyang, 110122, Liaoning, PR China.
  • 3 Precision Scientific (Beijing) Co., Ltd., 100085, Beijing, PR China.
  • 4 Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, 110122, Liaoning, PR China. [email protected].
  • # Contributed equally.
Abstract

Adenosine (A) to inosine (I) RNA editing catalyzed by adenosine deaminases acting on RNA (ADAR) enzymes is a post-transcriptional modification that emerged as a key player in tumorigenesis and Cancer progression. Antizyme inhibitor 1 (AZIN1) is one of the most frequent A-to-I RNA alterations in many human cancers. RNA-edited AZIN1 is known to confer a gain-of-function phenotype associated with aggressive tumors. However, the functional impact of RNA-edited AZIN1 in Cancer angiogenesis remains unexplored. We showed here that RNA-edited AZIN1 promoted tumor angiogenesis through the upregulation of IL-8 via in vitro and in vivo experiments. And we subsequently demonstrated that delaying c-Myc degradation by OAZ2-mediated ubiquitin-independent Proteasome pathway contributed to increase mRNA level and the secretion of angiogenic factor IL-8. Our study suggests an important contribution of RNA-edited AZIN1 to the tumor vascular microenvironment and highlights its translational potential. Thus, we revealed a potential approach to explore small-molecule antagonists such as reparixin attenuating IL-8 signaling for treatment of human Cancer patients detected with hyper-editing.

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