Golgi Phosphoprotein 3 Inhibits the Apoptosis of Human Glioma Cells in Part by Downregulating N-myc Downstream Regulated Gene 1

Abstract

BackgroundGolgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. Our previous study showed that GOLPH3 expression in glioma tissues was related to the severity of the malignancy of the cancer. However, the mechanism by which GOLPH3 affects cell apoptosis is largely unknown. The present study was designed to explore the possible mechanism of GOLPH3 in cell apoptosis.Material/MethodsTo analyze the biological role of GOLPH3 in glioma cells, we used GOLPH3 small interference RNA in apoptosis of glioma cells. The apoptosis of glioma cells was detected by flow cytometry. The expression level of GOLPH3 and NDRG1 protein was determined by Western blot analyses and immunohistochemical staining, respectively, to evaluate their association with glioma. Tumor tissues were collected from patients with glioma. Normal cerebral tissues were acquired from cerebral trauma patients undergoing internal decompression surgery.ResultsWe confirm that the decrease of GOLPH3 that promotes the apoptosis of glioma cells may be regulated by the activation of NDRG1 and cleaved capcase 3. There was a inverse association between GOLPH3 and NDRG1 in glioma samples.ConclusionsOur findings indicate that GOLPH3 and NDRG1 both play an important role in glioma etiology. Either GOLPH3 or NDRG1 might be a potential candidate for malignant glioma therapy.

Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer

“…As such, NDRG1 is considered a bona fide tumor suppressor. In a recent work [72], the authors showed that GOLPH3 knockdown in U251 promotes glioma cell apoptosis and increases cellular levels of both NDRG1 and cleaved caspase 3 by 55% and 80%, respectively. On the other hand, NDRG1 knockdown does not affect GOLPH3 expression but lowers the level of cleaved caspase 3, suggesting that GOLPH3 increases the cleavage of caspase 3 and apoptosis of glioma cells partially via downregulating NDRG1.…”

Golgi Structure and Function in Health, Stress, and Diseases

“…Depletion of GOLPH3 or MYO18A increases cancer cells' sensitivity to DNA damage inducing agents, suggesting that GOLPH3 phosphorylation-induced Golgi fragmentation may serve as a protective mechanism (Farber-Katz et al 2014). Considering that GOLPH3 is overexpressed in many solid tumors, it is reasonable to speculate that this may be a mechanism of how cancer cells escape DNA damage-induced apoptosis (Farber-Katz et al 2014;Buschman et al 2015;Li et al 2016b).…”

Correlation of NEDD4-1 and PTEN expression with the invasive capacity of pituitary adenomas

“…Following a general streptavidin-biotin complex immunohistochemical protocol (9), immunoreactivity was visualized with diaminobenzidine and the nuclei were counterstained with hematoxylin. Sections were then subsequently dehydrated in a series of graded alcohols, cleared in xylene and mounted.…”