Hypoxia-induced miR-210 promoter demethylation enhances proliferation, autophagy and angiogenesis of schwannoma cells.

Abstract

Hypoxia, a dominant feature in cancer occurrence and evolution, exists throughout the progression of most malignant tumors. This study focused on the mechanism of hypoxia-induced miR-210 upregulation, and the miR-210 functions in schwannoma. We detected microvascular density, vascular endothelial growth factor (VEGF) and miR-210 expression levels using schwannoma tissue mciroarray. The results showed that miR-210 expression was significantly associated with VEGF. Moreover, the cytological tests showed that hypoxia induced miR-210 expression, while reduce ephrin-A3 expression. The bisulfate genomic sequencing PCR results showed that miR-210 promoter region was hypermethylated in RT4-D6P2T in normoxia, while demethylated in hypoxia, and the region included the hypoxia-inducible factor-1α (HIF-1α) response element site. Cellular function research showed that hypoxia resulted in RT4-D6P2T apoptosis, higher autophage and invasion. Besides, hypoxia can affect HIF-1α/VEGF-mediated angiogenesis. To learn about the specific functions of miR-210, we found that with miR-210 inhibition, tumor cell apoptosis increased, autophagy and angiogenesis reduced, and the cell cycle was arrested. Hypoxia promoted miR-210 expression through promoter demethylation, then consequently enhanced tumor cell proliferation and autophagy, increasing tumor cell angiogenesis. Thus, miR-210 could be a potential marker for judging tumor malignancy and be taken as an effective target for clinical auxiliary treatment of neurilemmoma.

• Authors: Zhengguang Wang, Mingsi Deng, Zhendong Liu, Song Wu
• Journal: Oncology reports (Oncol Rep) Vol. 37 Issue 5 Pg. 3010-3018 (May 2017) ISSN: 1791-2431 [Electronic] Greece
• PMID: 28440459 (Publication Type: Journal Article)

Chemical References

• Ephrin-A3
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• MIRN210 microRNA, human
• MicroRNAs
• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Autophagy
• Cell Hypoxia
• Cell Line, Tumor
• Cell Proliferation
• DNA Methylation
• Ephrin-A3 (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• MicroRNAs (genetics)
• Neurilemmoma (blood supply, genetics)
• Promoter Regions, Genetic
• Up-Regulation
• Vascular Endothelial Growth Factor A (genetics)