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

Wang,Zhengguang; Deng,Mingsi; Liu,Zhendong; Wu,Song

doi:10.3892/or.2017.5511

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

Authors:
- Zhengguang Wang
- Mingsi Deng
- Zhendong Liu
- Song Wu
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Affiliations: Department of Orthopaedic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Orthodontics, The Stomatological Hospital of Changsha, Changsha, Hunan 410005, P.R. China
Published online on: March 16, 2017 https://doi.org/10.3892/or.2017.5511
Pages: 3010-3018

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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.

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