Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy

Abstract

Glioma is the most common primary malignant intracranial tumor. Owing to highly aggressive invasiveness and metastatic properties, the prognosis of this disease remains poor even with surgery, radiotherapy, and chemotherapy. Rutin is a glycoside natural flavonoid that modulates microglia inflammatory profile and improves anti-glioma activity. Here, a glycoside flavonoid was extracted and named purple sweet potato delphinidin-3-rutin (PSPD3R). In an experiment using the subcutaneous xenograft model of human glioblastoma (GBM) and alamar blue assay, we found that PSPD3R suppressed the glioma proliferation both in vitro and in vivo. Flow cytometry assay and transmission electron microscopy observation revealed that PSPD3R stimulated glioma cell autophagy and apoptosis. High-throughput microRNA (miRNA) sequencing showed that PSPD3R substantially affected the miRNA expression of U251 cells. Acridine orange staining and immunoblotting indicated that PSPD3R regulated autophagy via Akt/Creb/miR-20b-5p in glioma cells. Luciferase reporter assays showed that autophagy-related gene 7 (Atg7) mRNA was the target gene of miR-20b-5p. The downregulation of miR-20b-5p inhibited glioma proliferation in vivo. In summary, PSPD3R regulated autophagy in glioma via the Akt/Creb/miR-20b-5p/Atg7 axis. This work unraveled the molecular mechanism of PSPD3R-induced autophagy in glioma and revealed its potential as a therapeutic agent for glioma treatment.

Keywords

• glioma
• rutin
• autophagy
• miRNA-20b-5p
• Creb
• Atg7