MicroRNA-576-3p inhibits the migration and proangiogenic abilities of hypoxia-treated glioma cells through hypoxia-inducible factor-1α

摘要

The most common and aggressive type of brain cancer in adults is glioblastoma multiforme (GBM), and hypoxia is a common feature of glioblastoma. As the histological features of glioma include capillary endothelial cell proliferation, they are highly prone to invading the surrounding normal brain tissue, which is often one of the reasons for the failure of treatment. However, the mechanisms involved in this process are not fully understood. MicroRNAs (miRs) are a class of non-coding RNA that are able to inhibit the malignant progression of tumor cells through the regulation of downstream genes. In the present study, the low expression of miR-576-3p was detected in glioma samples and hypoxia-treated glioma cells using a reverse transcription-quantitative polymerase chain reaction. The present study focused on the effects of miR-576-3p on hypoxia-induced glioma. The results of the functional experiments revealed that the overexpression of miR-576-3p significantly inhibited the migration and pro-angiogenic abilities of the glioma cells under hypoxic conditions (P<0.05) compared with in the lentivirus-miR-negative control group. Furthermore, luciferase reporter gene assays were used to validate the hypothesis that miR-576-3p interacts with the 3′-untranslated region of hypoxia-inducible factor-1α (HIF-1α) and induces a reduction in the protein levels of matrix metalloproteinase-2 and vascular endothelial growth factor. Rescue experiments demonstrated that the restoration of HIF-1α expression attenuated the effect of miR-576-3p on the migration and proangiogenic abilities of glioma cells. In conclusion, the present study confirms that miR-576-3p is a novel GBM inhibitor and its inhibition of the migration and proangiogenic capacity of hypoxia-induced glioma cells is mediated by HIF-1α.