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Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways.

ABSTRACT: Autophagy is a major intracellular degradation system that plays an important role in several biological processes. Although some studies indicate that autophagy may play a role in lens degradation and cataracts formation, its underlying mechanism remains to be elucidated. Autophagy?related gene 4a (ATG4a) cleaves autophagy?related protein 8 (Atg8) near the C terminus, allowing Atg8 to conjugate with phosphatidylethanolamine via the exposed glycine; although this is pivotal in cancer development, no study has yet linked it to eye diseases. In the present study, the protein expression of ATG4a is significantly upregulated in hydrogen peroxide?treated lens epithelial cells (HLE?B3), indicating that ATG4a may play an important role in lens degradation. ATG4a was overexpressed using lentivirus in lens epithelial cells to observe the effect of ATG4a on various phenotypes by transmission electron microscopy, western blotting, EdU incorporation assay, flow cytometry and in situ cell death detection. The results demonstrated that the overexpression of ATG4a could promote autophagy by promoting the adenosine 5'?monophosphate?activated protein kinase pathway and inhibiting the Akt pathway. It also upregulated the proliferation and downregulated the apoptosis of lens epithelial cells. Overall, the present study showed that ATG4a plays a vital role in lens degradation and that it could be a potential target in cataract therapies.

SUBMITTER: Yan C

PROVIDER: S-EPMC7339427 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways.

Yan Chufan C Zhao Jiangyue J Qin Yu Y Zhao Fangkun F Ji Liyang L Zhang Jinsong J

Molecular medicine reports 20200602 2

Autophagy is a major intracellular degradation system that plays an important role in several biological processes. Although some studies indicate that autophagy may play a role in lens degradation and cataracts formation, its underlying mechanism remains to be elucidated. Autophagy‑related gene 4a (ATG4a) cleaves autophagy‑related protein 8 (Atg8) near the C terminus, allowing Atg8 to conjugate with phosphatidylethanolamine via the exposed glycine; although this is pivotal in cancer development ...[more]

PMID: 32626969

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Project description:BackgroundGBM is the most frequent malignant primary brain tumor in humans. The CLEC19A is a member of the C-type lectin family, which has a high expression in brain tissue. Herein, we sought to carry out an in-depth analysis to pinpoint the role of CLEC19A expression in GBM.MethodsTo determine the localization of CLEC19A, this protein was detected using Western blot, Immunocytochemistry/Immunofluorescence, and confocal microscopy imaging. CLEC19A expression in glioma cells and tissues was evaluated by qRT-PCR. Cell viability, proliferation, migration, and apoptosis were examined through MTT assay, CFSE assay, colony formation, wound healing assay, transwell test, and flow cytometry respectively after CLEC19A overexpression. The effect of CLEC19A overexpression on the PI3K/AKT/NF-κB signaling pathway was investigated using Western blot. An in vivo experiment substantiated the in vitro results using the glioblastoma rat models.ResultsOur in-silico analysis using TCGA data and measuring CLEC19A expression level by qRT-PCR determined significantly lower expression of CLEC19A in human glioma tissues compared to healthy brain tissues. By employment of ICC/IF, confocal microscopy imaging, and Western blot we could show that CLEC19A is plausibly a secreted protein. Results obtained from several in vitro readouts showed that CLEC19A overexpression in U87 and C6 glioma cell lines is associated with the inhibition of cell proliferation, viability, and migration. Further, qRT-PCR and Western blot analysis showed CLEC19A overexpression could reduce the expression levels of PI3K, VEGFα, MMP2, and NF-κB and increase PTEN, TIMP3, RECK, and PDCD4 expression levels in glioma cell lines. Furthermore, flow cytometry results revealed that CLEC19A overexpression was associated with significant cell cycle arrest and promotion of apoptosis in glioma cell lines. Interestingly, using a glioma rat model we could substantiate that CLEC19A overexpression suppresses glioma tumor growth.ConclusionsTo our knowledge, this is the first report providing in-silico, molecular, cellular, and in vivo evidences on the role of CLEC19A as a putative tumor suppressor gene in GBM. These results enhance our understanding of the role of CLEC19A in glioma and warrant further exploration of CLEC19A as a potential therapeutic target for GBM.

Dataset Information

Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways.

Publications

Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways.

Similar Datasets

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