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Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy

Authors: Chunhui Hu, Beibei Chen, Yibin Zhou, Yuxi Shan

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

Ras-related protein 25 (Rab25) functions either as an oncogene or a tumor suppressor with a cancer type-dependent manner. We aimed to investigate clinical significance of Rab25 in prostate cancer (PCa).

Methods

Quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were respectively performed to detect Rab25 mRNA and protein expression in PCa and adjacent non-cancerous prostate tissues. Receiver-operating characteristic curve analysis was used to evaluate predictive diagnostic value of Rab25. Associations of Rab25 expression with various clinicopathological characteristics and biochemical recurrence-free survival of PCa patients were statistically evaluated. In vitro, PCa cell proliferation was assessed by CCK-8 assay, and the cell migration and invasion activities were evaluated by Transwell assay, following the transfection of Rab25 small interfering RNA.

Results

Ras-related protein 25 mRNA and protein expression in PCa tissues were both significantly higher than adjacent non-cancerous prostate tissues (both P < 0.001). The area under the curve of Rab25 immunoreactive score (IRS) was 0.896 (P < 0.001) with 74.0% sensitivity and 95.0% specificity. High Rab25 IRS was significantly associated with high Gleason score (P = 0.02) and distant metastasis (P = 0.01). PCa patients with high Rab25 IRS had shorter overall and biochemical recurrence-free survivals than those with low Rab25 IRS (both P < 0.001). Cox regression analysis identified Rab25 as an independent biomarker for both overall and biochemical recurrence-free survivals of PCa patients. By exploring its activities in vitro, Rab25 downregulation was found to inhibit PCa cell proliferation, migration and invasion.

Conclusions

High expression of Rab25 may contribute to malignant progression and biochemical recurrence of PCa patients after radical prostatectomy.
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Literature
1.
go back to reference Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. Cancer J Clin. 2014;64:9–12.CrossRef Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. Cancer J Clin. 2014;64:9–12.CrossRef
2.
go back to reference Lanchon C, Shariat SF, Rouprêt M. The role for surgery in high-risk prostate cancer. Wien Med Wochenschr. 2015;165:395–400.CrossRefPubMed Lanchon C, Shariat SF, Rouprêt M. The role for surgery in high-risk prostate cancer. Wien Med Wochenschr. 2015;165:395–400.CrossRefPubMed
3.
go back to reference Wadosky KM, Koochekpour S. Therapeutic rationales, progresses, failures, and future directions for advanced prostate cancer. Int J Biol Sci. 2016;12:409–26.CrossRefPubMedPubMedCentral Wadosky KM, Koochekpour S. Therapeutic rationales, progresses, failures, and future directions for advanced prostate cancer. Int J Biol Sci. 2016;12:409–26.CrossRefPubMedPubMedCentral
4.
go back to reference Wang D, Yang T, Zou Y, Yang X. Analysis of the correlationship between prostate specific antigen related variables and risk factor in patients with prostate carcinoma. Cancer Transl Med. 2015;1(3):77–9.CrossRef Wang D, Yang T, Zou Y, Yang X. Analysis of the correlationship between prostate specific antigen related variables and risk factor in patients with prostate carcinoma. Cancer Transl Med. 2015;1(3):77–9.CrossRef
5.
6.
go back to reference Goldenring JR, Shen KR, Vaughan HD, Modlin IM. Identification of a small GTP-binding protein, Rab25, expressed in the gastrointestinal mucosa, kidney, and lung. J Biol Chem. 1993;68:18419–22. Goldenring JR, Shen KR, Vaughan HD, Modlin IM. Identification of a small GTP-binding protein, Rab25, expressed in the gastrointestinal mucosa, kidney, and lung. J Biol Chem. 1993;68:18419–22.
7.
go back to reference Casanova JE, Wang X, Kumar R, Bhartur SG, Navarre J, Woodrum JE, Altschuler Y, Ray GS, Goldenring JR. Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells. Mol Biol Cell. 1999;10:47–61.CrossRefPubMedPubMedCentral Casanova JE, Wang X, Kumar R, Bhartur SG, Navarre J, Woodrum JE, Altschuler Y, Ray GS, Goldenring JR. Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells. Mol Biol Cell. 1999;10:47–61.CrossRefPubMedPubMedCentral
8.
go back to reference Mitra S, Molina J, Mills GB, Dennison JB. Characterization of the role Rab25 in energy metabolism and cancer using extracellular flux analysis and material balance. Methods Mol Biol. 2015;1298:195–205.CrossRefPubMed Mitra S, Molina J, Mills GB, Dennison JB. Characterization of the role Rab25 in energy metabolism and cancer using extracellular flux analysis and material balance. Methods Mol Biol. 2015;1298:195–205.CrossRefPubMed
9.
go back to reference Cao C, Lu C, Xu J, Zhang J, Zhang J, Li M. Expression of Rab25 correlates with the invasion and metastasis of gastric cancer. Chin J Cancer Res. 2013;25:192–9.PubMedPubMedCentral Cao C, Lu C, Xu J, Zhang J, Zhang J, Li M. Expression of Rab25 correlates with the invasion and metastasis of gastric cancer. Chin J Cancer Res. 2013;25:192–9.PubMedPubMedCentral
10.
go back to reference Gomez-Roman N, Sahasrabudhe NM, McGregor F, Chalmers AJ, Cassidy J, Plumb J. Hypoxia-inducible factor 1 alpha is required for the tumourigenic and aggressive phenotype associated with Rab25 expression in ovarian cancer. Oncotarget. 2016;7:22650–64.PubMedPubMedCentral Gomez-Roman N, Sahasrabudhe NM, McGregor F, Chalmers AJ, Cassidy J, Plumb J. Hypoxia-inducible factor 1 alpha is required for the tumourigenic and aggressive phenotype associated with Rab25 expression in ovarian cancer. Oncotarget. 2016;7:22650–64.PubMedPubMedCentral
11.
go back to reference Nikoshkov A, Broliden K, Attarha S, Sviatoha V, Hellström AC, Mints M, Andersson S. Expression pattern of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes in normal and cancer cervical tissues. Int J Oncol. 2015;46:107–12.PubMed Nikoshkov A, Broliden K, Attarha S, Sviatoha V, Hellström AC, Mints M, Andersson S. Expression pattern of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes in normal and cancer cervical tissues. Int J Oncol. 2015;46:107–12.PubMed
12.
go back to reference Zhang J, Wei J, Lu J, Tong Z, Liao B, Yu B, Zheng F, Huang X, Chen Z, Fang Y, Li B, Chen W, Xie D, Luo J. Overexpression of Rab25 contributes to metastasis of bladder cancer through induction of epithelial-mesenchymal transition and activation of Akt/GSK-3β/Snail signaling. Carcinogenesis. 2013;34:2401–8.CrossRefPubMed Zhang J, Wei J, Lu J, Tong Z, Liao B, Yu B, Zheng F, Huang X, Chen Z, Fang Y, Li B, Chen W, Xie D, Luo J. Overexpression of Rab25 contributes to metastasis of bladder cancer through induction of epithelial-mesenchymal transition and activation of Akt/GSK-3β/Snail signaling. Carcinogenesis. 2013;34:2401–8.CrossRefPubMed
13.
go back to reference Li Y, Jia Q, Zhang Q, Wan Y. Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma. Biochem Biophys Res Commun. 2015;458:745–50.CrossRefPubMed Li Y, Jia Q, Zhang Q, Wan Y. Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma. Biochem Biophys Res Commun. 2015;458:745–50.CrossRefPubMed
14.
go back to reference Téllez-Gabriel M, Arroyo-Solera I, León X, Gallardo A, López M, Céspedes MV, Casanova I, López-Pousa A, Quer M, Mangues MA, Barnadas A, Mangues R, Pavón MA. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma. Cancer Med. 2013;2:950–63.CrossRefPubMedPubMedCentral Téllez-Gabriel M, Arroyo-Solera I, León X, Gallardo A, López M, Céspedes MV, Casanova I, López-Pousa A, Quer M, Mangues MA, Barnadas A, Mangues R, Pavón MA. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma. Cancer Med. 2013;2:950–63.CrossRefPubMedPubMedCentral
15.
go back to reference Mitra S, Federico L, Zhao W, Dennison J, Sarkar TR, Zhang F, Takiar V, Cheng KW, Mani S, Lee JS, Mills GB. Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT. Oncotarget. 2016;7:40252–65.PubMedPubMedCentral Mitra S, Federico L, Zhao W, Dennison J, Sarkar TR, Zhang F, Takiar V, Cheng KW, Mani S, Lee JS, Mills GB. Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT. Oncotarget. 2016;7:40252–65.PubMedPubMedCentral
16.
go back to reference Goldenring JR, Nam KT. Rab25 as a tumour suppressor in colon carcinogenesis. Br J Cancer. 2011;104:33–6.CrossRefPubMed Goldenring JR, Nam KT. Rab25 as a tumour suppressor in colon carcinogenesis. Br J Cancer. 2011;104:33–6.CrossRefPubMed
17.
go back to reference Kessler D, Gruen GC, Heider D, Morgner J, Reis H, Schmid KW, Jendrossek V. The action of small GTPases Rab11 and Rab25 in vesicle trafficking during cell migration. Cell Physiol Biochem. 2012;29:647–56.CrossRefPubMed Kessler D, Gruen GC, Heider D, Morgner J, Reis H, Schmid KW, Jendrossek V. The action of small GTPases Rab11 and Rab25 in vesicle trafficking during cell migration. Cell Physiol Biochem. 2012;29:647–56.CrossRefPubMed
18.
go back to reference Chang SS, Amin MB. Utilizing the tumor-node-metastasis staging for prostate cancer: the sixth edition, 2002. CA Cancer J Clin. 2008;58:54–9.CrossRefPubMed Chang SS, Amin MB. Utilizing the tumor-node-metastasis staging for prostate cancer: the sixth edition, 2002. CA Cancer J Clin. 2008;58:54–9.CrossRefPubMed
19.
20.
go back to reference Liu L, Ding G. Rab25 expression predicts poor prognosis in clear cell renal cell carcinoma. Exp Ther Med. 2014;8:1055–8.PubMedPubMedCentral Liu L, Ding G. Rab25 expression predicts poor prognosis in clear cell renal cell carcinoma. Exp Ther Med. 2014;8:1055–8.PubMedPubMedCentral
21.
go back to reference Zhang C, Liu Z, Wang L, Qiao B, Du E, Li L, Xu Y, Zhang Z. Prognostic significance of GPC5 expression in patients with prostate cancer. Tumour Biol. 2016;37:6413–8.CrossRefPubMed Zhang C, Liu Z, Wang L, Qiao B, Du E, Li L, Xu Y, Zhang Z. Prognostic significance of GPC5 expression in patients with prostate cancer. Tumour Biol. 2016;37:6413–8.CrossRefPubMed
22.
go back to reference Deneka M, Neeft M, van der Sluijs P. Regulation of membrane transport by rab GTPases. Crit Rev Biochem Mol Biol. 2003;38:121–42.CrossRefPubMed Deneka M, Neeft M, van der Sluijs P. Regulation of membrane transport by rab GTPases. Crit Rev Biochem Mol Biol. 2003;38:121–42.CrossRefPubMed
24.
go back to reference He H, Dai F, Yu L, She X, Zhao Y, Jiang J, Chen X, Zhao S. Identification and characterization of nine novel human small GTPases showing variable expressions in liver cancer tissues. Gene Expr. 2002;10:231–42.CrossRefPubMed He H, Dai F, Yu L, She X, Zhao Y, Jiang J, Chen X, Zhao S. Identification and characterization of nine novel human small GTPases showing variable expressions in liver cancer tissues. Gene Expr. 2002;10:231–42.CrossRefPubMed
25.
go back to reference Geng D, Zhao W, Feng Y, Liu J. Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion. Tumour Biol. 2016;37:7713–8.CrossRefPubMed Geng D, Zhao W, Feng Y, Liu J. Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion. Tumour Biol. 2016;37:7713–8.CrossRefPubMed
26.
go back to reference Ma YF, Yang B, Li J, Zhang T, Guo JT, Chen L, Li M, Chu J, Liang CY, Liu Y. Expression of Ras-related protein 25 predicts chemotherapy resistance and prognosis in advanced non-small cell lung cancer. Genet Mol Res. 2015;14:13998–4008.CrossRefPubMed Ma YF, Yang B, Li J, Zhang T, Guo JT, Chen L, Li M, Chu J, Liang CY, Liu Y. Expression of Ras-related protein 25 predicts chemotherapy resistance and prognosis in advanced non-small cell lung cancer. Genet Mol Res. 2015;14:13998–4008.CrossRefPubMed
Metadata
Title
High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy
Authors
Chunhui Hu
Beibei Chen
Yibin Zhou
Yuxi Shan
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0411-0

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