ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma

In this study, we found that ALKBH5, a key component of the N(6)-methyladenosine (m(6)A) 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 w...

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Detalles Bibliográficos
Autores principales: Hao, Lili, Yin, Jiayang, Yang, Hong, Li, Chaoxuan, Zhu, Linxin, Liu, Lian, Zhong, Jingxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906204/
https://www.ncbi.nlm.nih.gov/pubmed/33428593
http://dx.doi.org/10.18632/aging.202371
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author Hao, Lili
Yin, Jiayang
Yang, Hong
Li, Chaoxuan
Zhu, Linxin
Liu, Lian
Zhong, Jingxiang
author_facet Hao, Lili
Yin, Jiayang
Yang, Hong
Li, Chaoxuan
Zhu, Linxin
Liu, Lian
Zhong, Jingxiang
author_sort Hao, Lili
collection PubMed
description In this study, we found that ALKBH5, a key component of the N(6)-methyladenosine (m(6)A) 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 m(6)A demethylation of FOXM1 mRNA promotes UM progression. Therefore, AKLBH5 is a potential prognostic biomarker and therapeutic target in UM.
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spelling pubmed-79062042021-03-04 ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma Hao, Lili Yin, Jiayang Yang, Hong Li, Chaoxuan Zhu, Linxin Liu, Lian Zhong, Jingxiang Aging (Albany NY) Research Paper In this study, we found that ALKBH5, a key component of the N(6)-methyladenosine (m(6)A) 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 m(6)A demethylation of FOXM1 mRNA promotes UM progression. Therefore, AKLBH5 is a potential prognostic biomarker and therapeutic target in UM. Impact Journals 2021-01-10 /pmc/articles/PMC7906204/ /pubmed/33428593 http://dx.doi.org/10.18632/aging.202371 Text en Copyright: © 2021 Hao et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Hao, Lili
Yin, Jiayang
Yang, Hong
Li, Chaoxuan
Zhu, Linxin
Liu, Lian
Zhong, Jingxiang
ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma
title ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma
title_full ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma
title_fullStr ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma
title_full_unstemmed ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma
title_short ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma
title_sort alkbh5-mediated m(6)a demethylation of foxm1 mrna promotes progression of uveal melanoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906204/
https://www.ncbi.nlm.nih.gov/pubmed/33428593
http://dx.doi.org/10.18632/aging.202371
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