Increased Expression of GOLPH3 is Associated with the Proliferation of Prostate Cancer

Abstract

Background: Golgi phosphoprotein 3 (GOLPH3) is a metastasis-associated gene, however its role in cell proliferation of prostate cancer (PCa) has not yet been elucidated.Methods: The level of expression of GOLPH3 and other genes was examined by quantitative real-time PCR (QPCR) and western blot analysis. Furthermore, we performed a comprehensive analysis of the expression of GOLPH3 in PCa using a tissue microarray (TMA) and correlated our findings with pathological parameters of PCa. RNA interference (RNAi) was used to silence the expression of GOLPH3 in PC-3 cells and to measure the effects on proliferation and cell cycle using the CCK-8 assay and flow cytometry. Western blots were also employed to assess AKT-mTOR and cell cycle-related proteins.Results: We showed that the expression of GOLPH3 was located at the trans-Golgi membranes in PCa cells. We found that GOLPH3 was expressed in all PCa cells and was significantly higher in two androgen-independent cell lines, DU145 and PC-3. TMA immunohistochemistry showed that GOLPH3 was positive in 64% of cancer tissue samples compared with 20% in normal and 30% in benign samples (P<0.05). In vitro, silencing GOLPH3 expression inhibited cell proliferation and arrested the cell cycle at the G2/M phase. Silencing GOLPH3 also activated P21 expression but suppressed the expression of CDK1/2 and cyclinB1 protein together with the phosphorylation of AKT and mTOR.Conclusions: The expression of the GOLPH3 protein was significantly elevated in PCa. GOLPH3 can promote cell proliferation by enhancing the activity of AKT-mTOR signaling. Altogether, these findings suggest that GOLPH3 play important roles in proliferation and cell cycle regulation in PCa and might serve as promising biomarkers for PCa progression as well as potential therapeutic targets.

GOLPH3 and YB-1 Are Novel Markers Correlating With Poor Prognosis in Prostate Cancer

“…In the current study, moderate/intense cytoplasmic expression of GOLPH3 protein was found in 25% of BPH and in 68.4% of PC tissues and the difference was statistically significant. This result was similar to a previous study that reported 30% positivity in BPH and 64% in PC samples [ 28 ] but higher than previous studies that detected moderate/intense GOLPH3 expression in 5% of BPH, 8% of HGPIN and 37-40.66% of PC [ 8 , 11 ]. Therefore, differences noted in the expression of GOLPH3 in PC compared with BPH and PIN may facilitate the clinical diagnoses of PC.…”

“…Similar to a previous study in castration-resistant PC, GOLPH3 expression was positively correlated with Gleason score, tumor stage and lymph node metastasis [ 11 ]. On the contrary, no significant associations were found with Gleason score or tumor stage [ 28 ]. Collectively, these observations suggest that GOLPH3 acts as an oncogene in PC and may be a useful target for therapeutic interventions [ 11 , 28 , 29 ].…”

Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer

“…An increasing number of papers has shown that GOLPH3 drives cancer in several other solid tumors such as Neuroblastoma (NB) [42], Non-Small Cell Lung Cancer (NSLC) [89], epithelial ovarian carcinoma [90], prostate cancer [91,92], gastric cancer [93], and hepatocellular carcinoma [94,95] ( Figure 2). Recent reports indicate that GOLPH3 overexpression can be used as a positive biomarker for tumor progression and poor survival in these cancer types [89][90][91][92][93][94][95][96][97][98]. Experimental data in cancer cell lines or in nude mice revealed the role of GOLPH3 in cell proliferation, metastasis formation and angiogenesis ( Figure 2).…”

The Dual Role of miR-186 in Cancers: Oncomir Battling With Tumor Suppressor miRNA

“…In prostate cancer, miR-186 repressed cell proliferation via targeting YY1 and CDK6 (23) or GOLPH3 (22). Downregulation of GOLPH3 enhanced p21 expression and repressed the expression of Cyclin B1 and CDK1/2, thus blocking G1/S transition (73). MiR-186 repressed invasion and migration of prostate cancer cells by targeting Twist 1 (24).…”