Research Paper Volume 13, Issue 3 pp 4045—4062
ALKBH5-mediated m6A demethylation of FOXM1 mRNA promotes progression of uveal melanoma
- 1 Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China
Received: March 4, 2020 Accepted: September 9, 2020 Published: January 10, 2021https://doi.org/10.18632/aging.202371
How to Cite
Copyright: © 2021 Hao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
In this study, we found that ALKBH5, a key component of the N6-methyladenosine (m6A) methyltransferase complex, was significantly elevated in uveal melanoma (UM) cell lines and that ALKBH5 downregulation inhibited tumor growth in vivo. High ALKBH5 expression predicted worse outcome in patients with UM. EP300-induced H3K27 acetylation activation increased ALKBH5 expression. Downregulation of ALKBH5 inhibited UM cell proliferation, migration, and invasion and increased apoptosis in vitro. Besides, ALKBH5 may promote UM metastasis by inducing epithelial-to-mesenchymal transition (EMT) via demethylation of FOXM1 mRNA, which increases its expression and stability. In sum, our study indicates that AKLBH5-induced m6A demethylation of FOXM1 mRNA promotes UM progression. Therefore, AKLBH5 is a potential prognostic biomarker and therapeutic target in UM.