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Downregulation of MEG3 promotes neuroblastoma development through FOXO1-mediated autophagy and mTOR-mediated epithelial-mesenchymal transition.

ABSTRACT: Our previous studies demonstrated that MEG3 was significantly downregulated in neuroblastoma (NB) and its expression was negatively associated with the INSS stage. Overexpression of MEG3 promoted apoptosis and inhibited proliferation in NB cells. In this study, we discovered more potential functions and molecular mechanisms of MEG3 in NB. According to the database, MEG3 positively correlated with the NB survival rate and was negatively associated with malignant clinical features. Moreover, we determined that MEG3 was mainly located in the nucleus by nuclear-cytoplasmic separation and RNA fish assays. Upregulation of MEG3 in stably transfected cell lines was accomplished, and CCK8, colony formation, and EDU assays were performed, which indicated that MEG3 significantly suppressed cell proliferation. Both wound healing and transwell experiments demonstrated that MEG3 decreased cell migration and invasion. CHIRP enrichments showed the anticancer effects of MEG3 were probably linked to autophagy and the mTOR signaling pathway. LC3 fluorescence dots and western blots showed that MEG3 attenuated autophagy by inhibiting FOXO1, but not the mTOR signaling pathway. Furthermore, MEG3 inhibited metastasis through epithelial-mesenchymal transition via the mTOR signaling pathway. Consistent with the above results, downregulation of MEG3 facilitated NB malignant phenotypes. Mechanistically, MEG3 and EZH2 regulated each other via a negative feedback loop and promoted NB progression together. In conclusion, our findings suggested that MEG3 was a tumor suppressor in NB and could be a potential target for NB treatment in the future.

SUBMITTER: Ye M

PROVIDER: S-EPMC7545718 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Downregulation of MEG3 promotes neuroblastoma development through FOXO1-mediated autophagy and mTOR-mediated epithelial-mesenchymal transition.

Ye Mujie M Lu Hong H Tang Weitao W Jing Tianrui T Chen Shiyu S Wei Meng M Zhang Jingjing J Wang Jing J Ma Jing J Ma Duan D Dong Kuiran K

International journal of biological sciences 20201003 15

Our previous studies demonstrated that MEG3 was significantly downregulated in neuroblastoma (NB) and its expression was negatively associated with the INSS stage. Overexpression of MEG3 promoted apoptosis and inhibited proliferation in NB cells. In this study, we discovered more potential functions and molecular mechanisms of MEG3 in NB. According to the database, MEG3 positively correlated with the NB survival rate and was negatively associated with malignant clinical features. Moreover, we de ...[more]

PMID: 33061817

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Dataset Information

Downregulation of MEG3 promotes neuroblastoma development through FOXO1-mediated autophagy and mTOR-mediated epithelial-mesenchymal transition.

Publications

Downregulation of MEG3 promotes neuroblastoma development through FOXO1-mediated autophagy and mTOR-mediated epithelial-mesenchymal transition.

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