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

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.

Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm

“… hsa-miR-125b Associated with immune response of patients with ruptured intracranial aneurysms [ 85 ], upregulated in AAA subjects [ 44 ], suppresses bladder cancer development by targeting SIRT7 and MALAT1 [ 86 ]. hsa-miR-138 Promotes glioma angiogenesis through miR-138/HIF-1α/VEGF axis [ 87 ], upregulated after the induction of myocardial infarction [ 88 ]. hsa-miR-150 Inactivates VEGFA/VEGFR2 and the downstream Akt/mTOR signaling pathway in colorectal cancer [ 89 ], marker for early diagnosis of AMI [ 90 ], underexpression of this miRNA promotes proliferation and metastasis of gastric cancer [ 91 ].…”

The role of microenvironment in tumor angiogenesis

“…LncRNA UBE2CP3 promotes angiogenesis in hepatocellular carcinoma cells by activating ERK/HIF-1α/ VEGFA signaling [157]. LncRNA H19 binds to miR-138 through the mechanism of competing endogenous RNA (ceRNA), facilitating HIF-1α RNA stability and VEGFA expression to promote angiogenesis [158]. LncRNA H19 also interacts with miR199a-5p to increase VEGFA mRNA expression and promote angiogenesis [159].…”

Coding of Glioblastoma Progression and Therapy Resistance through Long Noncoding RNAs

“…In cell cultures, H19 promotes glioma-cell growth, invasion and proliferation, and angiogenesis. These tumor-promoting effects of H19 appear to be mediated through miR-675 [85], miR-29a [86], miR-140 [87], and miR-138/HIF-1α [88]. H19-derived miR-675 might regulate glioma-cell proliferation and migration through cyclin dependent kinase 6 (CDK6) and Cadherin 13 (CDH13), and predict poor prognosis for patients with glioma [89,90].…”