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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Melanoma | Research

m6A modification suppresses ocular melanoma through modulating HINT2 mRNA translation

Authors: Ruobing Jia, Peiwei Chai, Shanzheng Wang, Baofa Sun, Yangfan Xu, Ying Yang, Shengfang Ge, Renbing Jia, Yun-Gui Yang, Xianqun Fan

Published in: Molecular Cancer | Issue 1/2019

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Abstract

Background

Dynamic N6-methyladenosine (m6A) RNA modification generated and erased by N6-methyltransferases and demethylases regulates gene expression, alternative splicing and cell fate. Ocular melanoma, comprising uveal melanoma (UM) and conjunctival melanoma (CM), is the most common primary eye tumor in adults and the 2nd most common melanoma. However, the functional role of m6A modification in ocular melanoma remains unclear.

Methods

m6A assays and survival analysis were used to explore decreased global m6A levels, indicating a late stage of ocular melanoma and a poor prognosis. Multiomic analysis of miCLIP-seq, RNA-seq and Label-free MS data revealed that m6A RNA modification posttranscriptionally promoted HINT2 expression. RNA immunoprecipitation (RIP)-qPCR and dual luciferase assays revealed that HINT2 mRNA specifically interacted with YTHDF1. Furthermore, polysome profiling analysis indicated a greater amount of HINT2 mRNA in the translation pool in ocular melanoma cells with higher m6A methylation.

Results

Here, we show that RNA methylation significantly inhibits the progression of UM and CM. Ocular melanoma samples showed decreased m6A levels, indicating a poor prognosis. Changes in global m6A modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of methylated HINT2 mRNA, a tumor suppressor in ocular melanoma.

Conclusions

Our work uncovers a critical function for m6A methylation in ocular melanoma and provides additional insight into the understanding of m6A modification.
Appendix
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Metadata
Title
m6A modification suppresses ocular melanoma through modulating HINT2 mRNA translation
Authors
Ruobing Jia
Peiwei Chai
Shanzheng Wang
Baofa Sun
Yangfan Xu
Ying Yang
Shengfang Ge
Renbing Jia
Yun-Gui Yang
Xianqun Fan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1088-x

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