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

Abstract

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-κB-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-κB1 in an NF-κB1 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 Snai2 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.

• Authors: Zongze He, Juan Long, Chen Yang, Bo Gong, Meixiong Cheng, Qi Wang, Jian Tang
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 20 Pg. 20285-20307 (10 21 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 33085646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN21 microRNA, human
• MIRN23a microRNA, human
• MicroRNAs
• NF-kappa B p50 Subunit
• NFKB1 protein, human
• RNA, Long Noncoding
• SMAD7 protein, human
• Smad7 Protein
• long noncoding RNA DGCR5, human
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Animals
• Apoptosis
• Brain Neoplasms (enzymology, genetics, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Gene Expression Regulation, Neoplastic
• Glioma (enzymology, genetics, pathology)
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• NF-kappa B p50 Subunit (genetics, metabolism)
• Neoplasm Invasiveness
• PTEN Phosphohydrolase (metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• Signal Transduction
• Smad7 Protein (metabolism)
• Tumor Burden