期刊
CELL DEATH & DISEASE
卷 12, 期 4, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41419-021-03645-4
关键词
-
类别
资金
- National Natural Science Foundation of China [81772518, 81871904, 81902944]
- Interdisciplinary Program of Shanghai Jiao Tong University [YG2017MS58, ZH2018QNA51]
- Multicenter Clinical Trial of Shanghai JiaoTong University of medicine [DLY201602]
MALAT1 promotes IL-6 secretion in GC cells by blocking autophagic flux, leading to cancer progression. Mechanistically, MALAT1 competitively interacts with ELAVL1 to stabilize PTEN mRNA and activate the AKT/mTOR pathway, impacting autophagic flux.
Autophagy defection contributes to inflammation dysregulation, which plays an important role in gastric cancer (GC) progression. Various studies have demonstrated that long noncoding RNA could function as novel regulators of autophagy. Previously, long noncoding RNA MALAT1 was reported upregulated in GC cells and could positively regulate autophagy in various cancers. Here, we for the first time found that MALAT1 could promote interleukin-6 (IL-6) secretion in GC cells by blocking autophagic flux. Moreover, IL-6 induced by MALAT1 could activate normal to cancer-associated fibroblast conversion. The interaction between GC cells and cancer-associated fibroblasts in the tumour microenvironment could facilitate cancer progression. Mechanistically, MALAT1 overexpression destabilized the PTEN mRNA in GC cells by competitively interacting with the RNA-binding protein ELAVL1 to activate the AKT/mTOR pathway for impairing autophagic flux. As a consequence of autophagy inhibition, SQSTM1 accumulation promotes NF-kappa B translocation to elevate IL-6 expression. Overall, these results demonstrated that intercellular interaction between GC cells and fibroblasts was mediated by autophagy inhibition caused by increased MALAT1 that promotes GC progression, providing novel prevention and therapeutic strategies for GC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据