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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Research

m6A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma

Authors: Li Liu, Jing Wang, Guifeng Sun, Qiong Wu, Ji Ma, Xin Zhang, Nan Huang, Zhixuan Bian, Song Gu, Min Xu, Minzhi Yin, Fenyong Sun, Qiuhui Pan

Published in: Molecular Cancer | Issue 1/2019

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Abstract

Background

N6-Methyladenosine (m6A) modification has been implicated in many biological processes. It is important for the regulation of messenger RNA (mRNA) stability, splicing, and translation. However, its role in cancer has not been studied in detail. Here we investigated the biological role and underlying mechanism of m6A modification in hepatoblastoma (HB).

Methods

We used Reverse transcription quantitative real-time PCR (RT-qPCR) and Western blotting to determine the expression of m6A related factors. And we clarified the effects of these factors on HB cells using cell proliferation assay, colony formation, apoptotic assay. Then we investigated of methyltransferase-like 13 (METTL3) and its correlation with clinicopathological features and used xenograft experiment to check METTL3 effect in vivo. m6A-Seq was used to profiled m6A transcriptome-wide in hepatoblastoma tumor tissue and normal tissue. Finally, methylated RNA immunoprecipitation (MeRIP) assay, RNA remaining assay to perform the regulator mechanism of MEETL3 on the target CTNNB1 in HB.

Results

In this research, we discovered that m6A modifications are increased in hepatoblastoma, and METTL3 is the main factor involved with aberrant m6A modification. We also profiled m6A across the whole transcriptome in hepatoblastoma tumor tissues and normal tissues. Our findings suggest that m6A is highly expressed in hepatoblastoma tumors. Also, m6A is enriched not only around the stop codon, but also around the coding sequence (CDS) region. Gene ontology analysis indicates that m6A mRNA methylation contributes significantly to regulate the Wnt/β-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the CTNNB1.

Conclusion

Overall our findings suggest enhanced m6A mRNA methylation as an oncogenic mechanism in hepatoblastoma, METTL3 is significantly up-regulated in HB and promotes HB development. And identify CTNNB1 as a regulator of METTL3 guided m6A modification in HB.
Appendix
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Metadata
Title
m6A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma
Authors
Li Liu
Jing Wang
Guifeng Sun
Qiong Wu
Ji Ma
Xin Zhang
Nan Huang
Zhixuan Bian
Song Gu
Min Xu
Minzhi Yin
Fenyong Sun
Qiuhui Pan
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/s12943-019-1119-7

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