Aging
Navigate
Submit an Article
Research Paper|Volume 13, Issue 3|pp 4045—4062

ALKBH5-mediated m6A demethylation of FOXM1 mRNA promotes progression of uveal melanoma

Lili Hao1, Jiayang Yin1, Hong Yang1, Chaoxuan Li1, Linxin Zhu1, Lian Liu1, Jingxiang Zhong1
  • 1Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China
* Equal contribution
Received: March 4, 2020Accepted: September 9, 2020Published: January 10, 2021
https://doi.org/10.18632/aging.202371

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.

Abstract

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.