LncRNA MALAT1 promotes gastric cancer progression via inhibiting autophagic flux and inducing fibroblast activation

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 i...

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Bibliographic Details
Published in:Cell death & disease 2021-04, Vol.12 (4), p.368-368, Article 368
Main Authors: Wang, Zhenqiang, Wang, Xinjing, Zhang, Tianqi, Su, Liping, Liu, Bingya, Zhu, Zhenggang, Li, Chen
Format: Article
Language:English
Subjects:
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AKT protein
Antibodies
Autophagy
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Culture
Fibroblasts
Gastric cancer
Immunology
Interleukin 6
Life Sciences
Microenvironments
mRNA
NF-κB protein
Phagocytosis
PTEN protein
RNA-binding protein
TOR protein
Tumor microenvironment
Tumors
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Summary: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-κB 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.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-021-03645-4