4.6 Article

LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes

Journal

AGING-US
Volume 12, Issue 20, Pages 20285-20307

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/aging.103800

Keywords

glioma; lncRNA DGCR5; miR-21/Smad7 axis; miR-23a/PTEN axis

Funding

  1. Department of Science and Technology of Sichuan Province, China [2019YFS0399, 2017SZ0203]
  2. Foundation for Technology and Science Bureau of Chengdu, China [2018YF05-00336-SN]

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Glioma is one of the most commonly diagnosed brain malignancies with a high cancer-related death rate in humans. The prognosis of glioma patients is still unsatisfactory. In the present study, we attempted to identify lncRNAs and miRNAs that might be related to NF-kappa B-mediated epithelial-mesenchymal transition in glioma cells based on online microarray expression profiles, and investigate the specific effects of lncRNA-miRNA-mRNA axes on glioma cell phenotypes. Herein, we identified lncRNA DGCR5 as a downregulated lncRNA in glioma that was negatively regulated by NF-kappa B1 in an NF-kappa B1 RE-dependent manner. LncRNA DGCR5 overexpression significantly inhibited the capacity of glioma cells to proliferate, migrate, and invade, whereas promoted the apoptosis of glioma cells. Moreover, lncRNA DGCR5 overexpression upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker VIM, as well as Snail and TWIST. Regarding the underlying molecular mechanisms, lncRNA DGCR5 could inhibit miR-21 and miR-23a expression, and miR-21 or miR-23a overexpression significantly reversed the tumor-suppressive effects of lncRNA DGCR5 overexpression. LncRNA DGCR5 exerted its tumor-suppressive effects through the DGCR5/miR-21/Smad7 and DGCR5/miR-23a/PTEN axes. In conclusion, lncRNA DGCR5 suppresses the capacity of glioma cells to migrate and invade via miR-21/Smad7, whereas it inhibits the proliferation and enhances the apoptosis of glioma cells through miR-23a/PTEN.

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