m6A demethylase ALKBH5 restrains migration and invasion and Wnt signaling pathway activity of gastric cancer cells

Liting SHEN; Jinyang LI; Xianfeng LI; Linrong CHE; Kewei LIU; Qin LIU; Bin WANG; Zhongyi QIN; Dongfeng CHEN

doi:10.16016/j.1000-5404.202011217

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m⁶A demethylase ALKBH5 restrains migration and invasion and Wnt signaling pathway activity of gastric cancer cells

更新时间：2026-01-09

- m⁶A demethylase ALKBH5 restrains migration and invasion and Wnt signaling pathway activity of gastric cancer cells
- Journal of Third Military Medical University Vol. 43, Issue 6, Pages: 459-466(2021)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81672463);the Development Project of Key Laboratory of Tumor Immunopathology of Ministry of Education(2018jsz107)
- DOI：10.16016/j.1000-5404.202011217
  CLC：
- Received：23 November 2020，
  
  Published：30 March 2021
- 稿件说明：
移动端阅览
Liting SHEN, Jinyang LI, Xianfeng LI, et al. m⁶A demethylase ALKBH5 restrains migration and invasion and Wnt signaling pathway activity of gastric cancer cells[J]. Journal of Third Military Medical University, 2021, 43(6): 459-466.
DOI：

Liting SHEN, Jinyang LI, Xianfeng LI, et al. m⁶A demethylase ALKBH5 restrains migration and invasion and Wnt signaling pathway activity of gastric cancer cells[J]. Journal of Third Military Medical University, 2021, 43(6): 459-466. DOI： 10.16016/j.1000-5404.202011217.

摘要

Abstract

Objective

To investigate the effect of RNA demethylase ALKBH5 on migration and invasion of gastric cancer (GC) cells and its potential mechanism.

Methods

Cancer Genome Atlas (TCGA) was employed to determine the correlation of ALKBH5 expression variations with overall survival (OS) in GC patients (<italic>n</italic>=371). The mouse models of orthotopic transplantation and metastasis were established to evaluate the correlation of between ALKBH5 expression and GC cells metastasis. After ALKBH5 knockdown and overexpression cells were constructed

the effect of ALKBH5 on migration and invasion of GC cells was explored with Transwell chamber assay. Furthermore

m6AVAR online database (<a href="http://m6Avar.renlab.org/index.html" target="blank">http://m6Avar.renlab.org/index.html</a>) was used to predict the m6A modification sites of Wnt activating targets; Western blotting and quantitative real-time PCR (qRT-PCR) combined with actinomycin D were applied to detect the protein expression and mRNA stability of downstream targets in Wnt signaling pathway.

Results

TCGA analysis showed that GC patients with lower ALKBH5 expression had shorter OS time.

In vivo

experiments confirmed that the low expression of ALKBH5 was involved in the distant metastasis of GC cells

and knockdown of ALKBH5 promoted the migration and invasion of GC cells. m

A modification sites were found in the mRNAs of Wnt downstream targets MYC

CD44 and c-Met

and the absence of ALKBH5 indicated increased protein expression and mRNA stability of these molecules.

Conclusion

The loss of ALKBH5 expression promotes the migration and invasiveness of GC cells and sustains the activation of Wnt signaling pathway.

关键词

Keywords

references

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