LncRNA H19 promotes glioma angiogenesis through miR-138/HIF-1α/VEGF axis

Zheng-Zheng Liu, Yi-Fu Tian, Heng Wu, Shu-Yu Ouyang,  Wei-Lu Kuang

Abstract:

Glioma is one of the most common and aggressive malignant primary brain tumors with high recurrence rate and mortality rate and heavily depends on the angiogenesis. LncRNA H19 has many diverse biological functions, including the regulation of cell proliferation, differentiation and metabolism. Here, we aimed to investigate the molecular mechanism of lncRNA H19 affecting angiogenesis in glioma, which could help to uncover potential target for glioma therapy. RT-qPCR analysis was performed to detect the expression of lncRNA H19 and miR-138 in HEB, U87, A172 and U373 cell lines. MTT assay was used to evaluate the cell viability. To evaluate the migration and invasion after lncRNA H19 knockdown, Transwell and wound healing assay were employed. After lncRNA H19 knockdown, protein expression of HIF-1α and VEGF was detected by western blot and tube formation was assessed. For the prediction and validation of the interaction between lncRNA H19 and miR-138, bioinformatics and luciferase assay were performed. We investigated the regulatory roles and downstream molecular mechanisms of lncRNA H19 in glioma by H19 knockdown, which inhibited the proliferation, migration and angiogenesis of glioma cells. Moreover, miR-138 acted as a target of H19 as detected by luciferase reporter assays. Meanwhile, HIF-1α was also a target of miR-138 and miR-138 could also regulate the proliferation, migration and angiogenesis of glioma cells by targeting HIF-1α and affecting the expression of VEGF in turn. Our findings identified an upregulated lncRNA H19 in glioma cells, which could promote proliferation, migration, invasion and angiogenesis via miR-138/HIF-1α axis as a ceRNA. This study provided a new opportunity to advance our understanding in the potential mechanism of lncRNA in glioma angiogenesis.