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Targeting RNA editing of antizyme inhibitor 1: A potential oligonucleotide-based antisense therapy for cancer. | LitMetric

Targeting RNA editing of antizyme inhibitor 1: A potential oligonucleotide-based antisense therapy for cancer.

Mol Ther

Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore 117599, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore 117594, Singapore; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, Singapore 117594, Singapore. Electronic address:

Published: November 2021

AI Article Synopsis

Article Abstract

Dysregulated adenosine-to-inosine (A-to-I) RNA editing is implicated in various cancers. However, no available RNA editing inhibitors have so far been developed to inhibit cancer-associated RNA editing events. Here, we decipher the RNA secondary structure of antizyme inhibitor 1 (AZIN1), one of the best-studied A-to-I editing targets in cancer, by locating its editing site complementary sequence (ECS) at the 3' end of exon 12. Chemically modified antisense oligonucleotides (ASOs) that target the editing region of AZIN1 caused a substantial exon 11 skipping, whereas ECS-targeting ASOs effectively abolished AZIN1 editing without affecting splicing and translation. We demonstrate that complete 2'-O-methyl (2'-O-Me) sugar ring modification in combination with partial phosphorothioate (PS) backbone modification may be an optimal chemistry for editing inhibition. ASO3.2, which targets the ECS, specifically inhibits cancer cell viability in vitro and tumor incidence and growth in xenograft models. Our results demonstrate that this AZIN1-targeting, ASO-based therapeutics may be applicable to a wide range of tumor types.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571177PMC
http://dx.doi.org/10.1016/j.ymthe.2021.05.008DOI Listing

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