m6A去甲基化酶ALKBH5抑制胃癌细胞运动侵袭和Wnt信号通路活性的机制

沈李婷; 李金洋; 李先峰; 车林茸; 刘科伟; 刘琴; 王斌; 覃中毅; 陈东风

doi:10.16016/j.1000-5404.202011217

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m⁶A去甲基化酶ALKBH5抑制胃癌细胞运动侵袭和Wnt信号通路活性的机制

基础医学 | 更新时间：2026-01-09

- m⁶A去甲基化酶ALKBH5抑制胃癌细胞运动侵袭和Wnt信号通路活性的机制
- m⁶A demethylase ALKBH5 restrains migration and invasion and Wnt signaling pathway activity of gastric cancer cells
- 第三军医大学学报 2021年43卷第6期页码：459-466
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目(81672463);肿瘤免疫病理学教育部重点实验室开发课题(2018jsz107)
- DOI：10.16016/j.1000-5404.202011217
  中图分类号：
- 收稿：2020-11-23，
  
  纸质出版：2021-03-30
- 稿件说明：
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沈李婷, 李金洋, 李先峰, 等. m⁶A去甲基化酶ALKBH5抑制胃癌细胞运动侵袭和Wnt信号通路活性的机制[J]. 第三军医大学学报, 2021,43(6):459-466.

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.
沈李婷, 李金洋, 李先峰, 等. m⁶A去甲基化酶ALKBH5抑制胃癌细胞运动侵袭和Wnt信号通路活性的机制[J]. 第三军医大学学报, 2021,43(6):459-466. DOI： 10.16016/j.1000-5404.202011217.

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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