The HIF ‑1α/miR‑224‑3p/ATG5 axis affects cell mobility and chemosensitivity by regulating hypoxia‑induced protective autophagy in glioblastoma and astrocytoma.

The HIF‑1α/miR‑224‑3p/ATG5 axis affects cell mobility and chemosensitivity by regulating hypoxia‑induced protective autophagy in glioblastoma and astrocytoma. Oncol Rep. 2018 Dec 13;: Authors: Huang S, Qi P, Zhang T, Li F, He X Abstract Human glioblastoma is a malignant and aggressive primary human brain solid tumor characterized by severe hypoxia. Hypoxia can induce autophagy, which may result in chemoresistance and malignant progression of cancer cells. MicroRNAs (miRNAs) have been reported to modulate hypoxia‑induced autophagy in various types of cancers. In the present study, we observed that hypoxia‑inducible factor (HIF)‑1α expression was increased while miR‑224‑3p expression was decreased under hypoxia in a time‑dependent manner in glioma LN229 and astrocytoma U‑251MG cell lines, as deteced by western blot analysis and real‑time quantitative polymerase chain reaction. In addition, HIF‑1α knockout inhibited cell motility and chemosensitivity by negatively regulating the expression of miR‑224‑3p under a hypoxic condition by Transwell and MTT assay. Moreover, hypoxia increased the relative expression of ATG5 (autophagy‑related gene 5) and LC3 II/I with a decreased level of p62. These results were correlated with autophagy in a time‑dependent manner, suggesting that hypoxia induced autophagy in glioblastoma and astrocytoma cells. Through bioinformatic prediction and luciferase reporter assay, w...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research