Midkine promotes glioblastoma progression via PI3K-Akt signaling.

Abstract

BACKGROUND:

Our previous bioinformatics-based study found that midkine (MDK) was associated with poor prognosis of glioblastoma (GBM). However, the mechanism of MDK in GBM remains elusive.

METHODS:

A public GBM-related dataset and GBM tissues from our center were used validate the aberrant expression of MDK in GBM at the RNA and protein levels. The relationship between MDK expression and survival of GBM patients was also explored through survival analysis. Subsequently, we identified MDK-related GBM-specific genes using differential expression analysis. Functional enrichment analyses were performed to reveal their potential biological functions. CCK-8, 5-ethynyl-2'-deoxyuridine, and Matrigel-transwell assays were performed in GBM cell lines in which MDK was knocked out or overexpressed in order assess the effects of MDK on proliferation, migration, and invasion of GBM cells. Western blotting was performed to detect candidate proteins.

RESULTS:

Our study showed MDK is a promising diagnostic and prognostic biomarker for GBM because it is highly expressed in the disease and it is associated with poor prognosis. MDK is involved in various cancer-related pathways, such as PI3K-Akt signaling, the cell cycle, and VEGF signaling. A comprehensive transcriptional regulatory network was constructed to show the potential pathways through which MDK may be involved in GBM. In vitro, Overexpression of MDK augmented proliferation, migration, and invasion of GBM cell lines, whereas suppression of MDK led to the opposite effects. Furthermore, our study confirmed that MDK promotes the progression of GBM by activating the PI3K-Akt signaling pathway.

CONCLUSIONS:

Our present study proposes that MDK promotes GBM by activating the PI3K-Akt signaling pathway, and it describes a potential regulatory network involved.

• Authors: Beiquan Hu, Chao Qin, Li Li, Lei Wei, Xianlun Mo, Huasheng Fan, Yuanhua Lei, Feng Wei, Donghua Zou
• Journal: Cancer cell international (Cancer Cell Int) Vol. 21 Issue 1 Pg. 509 (Sep 23 2021) ISSN: 1475-2867 [Print] England
• PMID: 34556138 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).