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- Title
RNA Editing Enzyme ADAR1 Regulates METTL3 in an Editing Dependent Manner to Promote Breast Cancer Progression via METTL3/ARHGAP5/YTHDF1 Axis.
- Authors
Li, Yi; Wang, Ning-Xi; Yin, Chuan; Jiang, Shan-Shan; Li, Jia-Chu; Yang, Sheng-Yong
- Abstract
A-to-I RNA editing and m6A modification are two of the most prevalent types of RNA modifications controlling gene expression in mammals and play very important roles in tumorigenesis and tumor progression. However, the functional roles and correlations of these two RNA modifications remain to be further investigated in cancer. Herein, we show that ADAR1, an A-to-I RNA-editing enzyme, interacts with METTL3 and increases its protein level to promote the proliferation, migration and invasion of breast cancer cells through a mechanism connecting ADAR1, METTL3 and YTHDF1. We show that both ADAR1 and METTL3 are upregulated in breast cancer samples, and ADAR1 positively correlates with METTL3; ADAR1 edits METTL3 mRNA and changes its binding site to miR532-5p, leading to increased METTL3 protein, which further targets ARHGAP5, recognized by YTHDF1. Additionally, we show that loss of ADAR1 significantly inhibits breast cancer growth in vivo. Collectively, our findings identify the ADAR1–METTL3 axis as a novel, important pathway that connects A-to-I editing and m6A RNA modifications during breast cancer progression.
- Subjects
RNA editing; CATALYTIC RNA; CANCER invasiveness; RNA modification &; restriction; BREAST cancer; CANCER cells; CANCER cell migration
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 17, p9656
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23179656