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GOLPH3 is a novel marker of poor prognosis and a potential therapeutic target in human renal cell carcinoma.

Xue Y, Wu G, Liao Y, Xiao G, Ma X, Zou X, Zhang G, Xiao R, Wang X, Liu Q, Long D, Yang J, Xu H, Liu F, Liu M, Xie K, Huang R - Br. J. Cancer (2014)

Bottom Line: Clinicopathological analysis showed that GOLPH3 expression was significantly correlated with T stage (P<0.001), lymph-node status (P=0.003), distant metastasis (P<0.001), tumour-node-metastasis (TNM) stage (P<0.001), and Fuhman grade (P=0.001).Knockdown of the GOLPH3 expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumour growth in xenograft model mice.These results suggest that GOLPH3 expression is likely to have important roles in RCC development and progression, and that GOLPH3 is a prognostic biomarker and a promising therapeutic target for RCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, First Affiliated Hospital of Gannan Medical University, No. 23, Qing Nian Road, Ganzhou 341000, People's Republic of China.

ABSTRACT

Background: Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. The present study was conducted to investigate the expression of GOLPH3 and its prognostic significance in renal cell carcinoma (RCC). Meanwhile, the function of GOLPH3 in human RCC was further investigated in cell culture models.

Methods: Expression of GOLPH3 was examined in 43 fresh RCC tissues and paired adjacent normal renal tissues by real-time quantitative PCR and western blotting. Immunohistochemistry for GOLPH3 was performed on additional 218 RCC tissues. The clinical significance of GOLPH3 expression was analysed. Downregulation of GOLPH3 was performed using small-interfering RNA (siRNA) in Caki-1 and 786-O cells with high abundance of GOLPH3, and the effects of GOLPH3 silencing on cell proliferation, migration, invasion in vitro, and tumour growth in vivo were evaluated.

Results: Expression of GOLPH3 was upregulated in the majority of the RCC clinical tissue specimens at both mRNA and protein levels. Clinicopathological analysis showed that GOLPH3 expression was significantly correlated with T stage (P<0.001), lymph-node status (P=0.003), distant metastasis (P<0.001), tumour-node-metastasis (TNM) stage (P<0.001), and Fuhman grade (P=0.001). Expression of GOLPH3 was inversely correlated with both overall and recurrence-free survival of RCC patients. Multivariate analysis showed that GOLPH3 expression was an independent prognostic indicator for patient's survival. Knockdown of the GOLPH3 expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumour growth in xenograft model mice.

Conclusions: These results suggest that GOLPH3 expression is likely to have important roles in RCC development and progression, and that GOLPH3 is a prognostic biomarker and a promising therapeutic target for RCC.

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Expression of GOLPH3 protein and mRNA and GOLPH3 knockdown by GOLPH3 siRNA in RCC cell lines. (A and B) GOLPH3 protein and mRNA expression detected in several human RCC cell lines (Caki-1, 786-O, A498, OS-RC-2, and ACHN) as well as in a normal proximal tubule epithelial cell line HK-2 by western blotting and real-time quantitative PCR, respectively. (C) Real-time quantitative PCR analysis of GOLPH3 mRNA expression in Caki-1 and 786-O cells transfected with the specific siRNA targeting GOLPH3 for 48 h. *P<0.01, relative to control. (D) Western blot analysis of GOLPH3 protein expression in Caki-1 and 786-O cells transfected with the GOLPH3 siRNA for 48 h. Efficient depletion of GOLPH3 expression was verified.
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fig5: Expression of GOLPH3 protein and mRNA and GOLPH3 knockdown by GOLPH3 siRNA in RCC cell lines. (A and B) GOLPH3 protein and mRNA expression detected in several human RCC cell lines (Caki-1, 786-O, A498, OS-RC-2, and ACHN) as well as in a normal proximal tubule epithelial cell line HK-2 by western blotting and real-time quantitative PCR, respectively. (C) Real-time quantitative PCR analysis of GOLPH3 mRNA expression in Caki-1 and 786-O cells transfected with the specific siRNA targeting GOLPH3 for 48 h. *P<0.01, relative to control. (D) Western blot analysis of GOLPH3 protein expression in Caki-1 and 786-O cells transfected with the GOLPH3 siRNA for 48 h. Efficient depletion of GOLPH3 expression was verified.

Mentions: We also detect the expression of GOLPH3 mRNA and protein in several human RCC cell lines as well as in an immortalised normal human proximal tubule epithelial cell line. As presented in Figure 5A, Caki-1, 786-O, A498, OS-RC-2, and ACHN showed higher level of GOLPH3 mRNA relative to the HK-2 normal proximal tubule epithelial cell line. Consistent with the mRNA data, GOLPH3 protein was also elevated in those RCC cell lines compared with the HK-2 cell line (Figure 5B).


GOLPH3 is a novel marker of poor prognosis and a potential therapeutic target in human renal cell carcinoma.

Xue Y, Wu G, Liao Y, Xiao G, Ma X, Zou X, Zhang G, Xiao R, Wang X, Liu Q, Long D, Yang J, Xu H, Liu F, Liu M, Xie K, Huang R - Br. J. Cancer (2014)

Expression of GOLPH3 protein and mRNA and GOLPH3 knockdown by GOLPH3 siRNA in RCC cell lines. (A and B) GOLPH3 protein and mRNA expression detected in several human RCC cell lines (Caki-1, 786-O, A498, OS-RC-2, and ACHN) as well as in a normal proximal tubule epithelial cell line HK-2 by western blotting and real-time quantitative PCR, respectively. (C) Real-time quantitative PCR analysis of GOLPH3 mRNA expression in Caki-1 and 786-O cells transfected with the specific siRNA targeting GOLPH3 for 48 h. *P<0.01, relative to control. (D) Western blot analysis of GOLPH3 protein expression in Caki-1 and 786-O cells transfected with the GOLPH3 siRNA for 48 h. Efficient depletion of GOLPH3 expression was verified.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4007226&req=5

fig5: Expression of GOLPH3 protein and mRNA and GOLPH3 knockdown by GOLPH3 siRNA in RCC cell lines. (A and B) GOLPH3 protein and mRNA expression detected in several human RCC cell lines (Caki-1, 786-O, A498, OS-RC-2, and ACHN) as well as in a normal proximal tubule epithelial cell line HK-2 by western blotting and real-time quantitative PCR, respectively. (C) Real-time quantitative PCR analysis of GOLPH3 mRNA expression in Caki-1 and 786-O cells transfected with the specific siRNA targeting GOLPH3 for 48 h. *P<0.01, relative to control. (D) Western blot analysis of GOLPH3 protein expression in Caki-1 and 786-O cells transfected with the GOLPH3 siRNA for 48 h. Efficient depletion of GOLPH3 expression was verified.
Mentions: We also detect the expression of GOLPH3 mRNA and protein in several human RCC cell lines as well as in an immortalised normal human proximal tubule epithelial cell line. As presented in Figure 5A, Caki-1, 786-O, A498, OS-RC-2, and ACHN showed higher level of GOLPH3 mRNA relative to the HK-2 normal proximal tubule epithelial cell line. Consistent with the mRNA data, GOLPH3 protein was also elevated in those RCC cell lines compared with the HK-2 cell line (Figure 5B).

Bottom Line: Clinicopathological analysis showed that GOLPH3 expression was significantly correlated with T stage (P<0.001), lymph-node status (P=0.003), distant metastasis (P<0.001), tumour-node-metastasis (TNM) stage (P<0.001), and Fuhman grade (P=0.001).Knockdown of the GOLPH3 expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumour growth in xenograft model mice.These results suggest that GOLPH3 expression is likely to have important roles in RCC development and progression, and that GOLPH3 is a prognostic biomarker and a promising therapeutic target for RCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, First Affiliated Hospital of Gannan Medical University, No. 23, Qing Nian Road, Ganzhou 341000, People's Republic of China.

ABSTRACT

Background: Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. The present study was conducted to investigate the expression of GOLPH3 and its prognostic significance in renal cell carcinoma (RCC). Meanwhile, the function of GOLPH3 in human RCC was further investigated in cell culture models.

Methods: Expression of GOLPH3 was examined in 43 fresh RCC tissues and paired adjacent normal renal tissues by real-time quantitative PCR and western blotting. Immunohistochemistry for GOLPH3 was performed on additional 218 RCC tissues. The clinical significance of GOLPH3 expression was analysed. Downregulation of GOLPH3 was performed using small-interfering RNA (siRNA) in Caki-1 and 786-O cells with high abundance of GOLPH3, and the effects of GOLPH3 silencing on cell proliferation, migration, invasion in vitro, and tumour growth in vivo were evaluated.

Results: Expression of GOLPH3 was upregulated in the majority of the RCC clinical tissue specimens at both mRNA and protein levels. Clinicopathological analysis showed that GOLPH3 expression was significantly correlated with T stage (P<0.001), lymph-node status (P=0.003), distant metastasis (P<0.001), tumour-node-metastasis (TNM) stage (P<0.001), and Fuhman grade (P=0.001). Expression of GOLPH3 was inversely correlated with both overall and recurrence-free survival of RCC patients. Multivariate analysis showed that GOLPH3 expression was an independent prognostic indicator for patient's survival. Knockdown of the GOLPH3 expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumour growth in xenograft model mice.

Conclusions: These results suggest that GOLPH3 expression is likely to have important roles in RCC development and progression, and that GOLPH3 is a prognostic biomarker and a promising therapeutic target for RCC.

Show MeSH
Related in: MedlinePlus