N-myc Downstream-Regulated Gene 1 (NDRG1) Regulates Vascular Endothelial Growth Factor A (VEGFA) and Malignancies in Glioblastoma Multiforme (GBM)

Abstract

Background. NDRG1 has been reported to exhibit relatively low expression levels in glioma tissues compared with adjacent brain tissues. Additionally, NDRG1 is reported to be a tumor suppressor with the potential to suppress the proliferation, invasion, and migration of cancer cells. However, its exact roles in GBM are still unknown. Methods. Gene Expression Profiling Interactive Analysis (GEPIA) was employed to evaluate the expression level of NDRG1 in GBM. After the introduction of NDRG1, proliferation, analyses of colony formation, migration, and invasion capacities were performed. A luciferase reporter assay was performed to detect the effect of NDRG1 on the vascular endothelial growth factor A (VEGFA) promoter. Results. In this study, data from GBM and healthy individuals were retrospectively collected by employing GBM, and VEGFA was found to be differentially expressed in GBM tissues compared with adjacent brain tissues. Furthermore, NDRG1 expression is positively correlated with VEGFA expression, but not expression of the other two VEGF isoforms, VEGFB and VEGFC. In the glioma cell lines U87MG and U118, overexpression of NDRG1 significantly upregulated VEGFA. By performing a dual-luciferase reporter assay, it was observed that overexpressed NDRG1 transcriptionally activated VEGFA. Expectedly, overexpression of NDRG1 decreased cell viability by blocking cell cycle phases at G1 phase. Additionally, overexpression of NDRG1 inhibited invasion, colony formation, and tumor formation in soft agar. Remarkably, VEGFA silencing or blockade of VEGF receptor 2 (VEGFR2) further inhibited malignant behaviors in soft agar, including proliferation, invasion, colony formation, and tumor formation. Conclusions. NDRG1-induced VEGFA exerts protective effects in GBM via the VEGFA/VEGFR2 pathway. Therefore, targeting both NDRG1 and VEGFA may represent a novel therapy for the treatment of GBM.

CDCA3 is a prognostic biomarker for cutaneous melanoma and is connected with immune infiltration

“…According to studies by Chang et al, DNMT family DNA methylation may be the cause of the downregulation of NDRG1 expression in gastric cancer. Patients with stomach cancer may benefit from using a demethylating agent as a targeted medication (32). NDRG1 has significant scientific implications in both prostate cancer and glioblastoma (33,34).…”

“…Patients with stomach cancer may benefit from using a demethylating agent as a targeted medication ( 32 ). NDRG1 has significant scientific implications in both prostate cancer and glioblastoma ( 33 , 34 ).…”

Elevated expression of N-myc downstream regulated gene 1 protein promotes neovascularization and tumor progression in glioblastomas

“…NDRG1 expression in various tumors, including brain tumors, have been previously investigated [9][10][11][12][13][14][15][16][17][18][19][20][21][22][25][26][27][28][29][30][31]. NDRG1 acts as a tumor suppressor in tumors of the prostate, breast, and nervous system [21][22][23][24][25][26].…”

“…NDRG1 acts as a tumor suppressor in tumors of the prostate, breast, and nervous system [21][22][23][24][25][26]. However, it is predictive of a poor prognosis in patients with carcinomas of the lung, liver, urinary bladder, stomach, cervix, and esophagus [27][28][29][30][31]. This suggests that whether or not NDRG1 expression promotes tumor progression depends upon the type of neoplasm.…”

“…Although the signi cance of NDRG1 expression in gliomas, including GBs is controversial [22,[25][26][27][28][29][30][31],…”