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

Meng Wang; Ke Liu; Huimin Bu; Hao Cong; Guokai Dong; Nana Xu; Changgen Li; Yunyun Zhao; Fei Jiang; Yongjing Zhang; Bo Yuan; Rongpeng Li; Jihong Jiang

doi:10.1016/j.omto.2022.07.007

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

Mol Ther Oncolytics. 2022 Jul 31:26:314-329. doi: 10.1016/j.omto.2022.07.007. eCollection 2022 Sep 15.

Authors

Meng Wang^{1

2}, Ke Liu^{1

3}, Huimin Bu¹, Hao Cong¹, Guokai Dong¹, Nana Xu¹, Changgen Li¹, Yunyun Zhao¹, Fei Jiang¹, Yongjing Zhang¹, Bo Yuan¹, Rongpeng Li¹, Jihong Jiang^{1

4}

Affiliations

¹ Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province, School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, People's Republic of China.
² Public Experimental Research Center, Xuzhou Medical University, Xuzhou, Jiangsu 221004, People's Republic of China.
³ Xuzhou Administration for Market Regulation, Xuzhou, Jiangsu 221000, People's Republic of China.
⁴ College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, People's Republic of China.

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: Atg7; Creb; autophagy; glioma; miRNA-20b-5p; rutin.