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Long noncoding RNA NEAT1 promotes progression of glioma as a ceRNA by sponging miR‐185‐5p to stimulate DNMT1/mTOR signaling
Author(s) -
Yu Heng,
Xu Anchun,
Wu Bo,
Wang Meng,
Chen Zhongjun
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29644
Subject(s) - glioma , cancer research , pi3k/akt/mtor pathway , long non coding rna , gene knockdown , carcinogenesis , downregulation and upregulation , competing endogenous rna , biology , dnmt1 , oncogene , cell growth , signal transduction , methyltransferase , chemistry , microbiology and biotechnology , apoptosis , cancer , cell cycle , methylation , gene , biochemistry , genetics
Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) is regarded as an oncogene in multiple cancers. Previous studies have shown that NEAT1 is involved in the proliferation and tumorigenesis of glioma cells, while miR‐185‐5p functions as a tumor suppressor in glioma. However, the underlying molecular mechanism of NEAT1 in glioma, especially in association with miR‐185‐5p, has not been studied. In this study, we first demonstrated that NEAT1 expression was upregulated, and miR‐185‐5p downregulated in glioma tissues and cells. More important, NEAT1 expression was negatively correlated with miR‐185‐5p expression in glioma tissues. In vitro and in vivo experiments verified that NEAT1 was a competing endogenous RNA for miR‐185‐5p for promoting DNA methyltransferase 1 (DNMT1) expression and activated mammalian target of rapamycin (mTOR) signaling, thus inhibiting apoptosis, and promoting glioma migration, proliferation, and epithelial–mesenchymal transition process. Furthermore, NEAT1 knockdown suppressed tumor growth and reduced the expression of proliferation antigen Ki‐67, DNMT1, and mTOR, but upregulated the expression of miR‐185‐5p in vivo. Finally, with mTOR inhibitor rapamycin, we confirmed that NEAT1 promoted glioma activity through mTOR signaling both in vitro and in vivo. In conclusion, these results suggest that NEAT1 promotes glioma tumorigenesis via miR‐185‐5p/DNMT1/mTOR signaling, which may provide a new target for the diagnosis and therapy of glioma.