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Rab23 is overexpressed in human bladder cancer and promotes cancer cell proliferation and invasion

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Tumor Biology

Abstract

Rab23 overexpression has been implicated in several human cancers. However, its expression pattern and biological roles in human bladder cancer have not been elucidated. In this study, we examined Rab23 expression in 93 bladder cancer specimens and analyzed its correlation with clinicopathological parameters. We found that Rab23 was overexpressed in 45 of 93 (48.3 %) cancer specimens. Significant association was found between Rab23 overexpression and tumor invasion depth (p = 0.0027). Rab23 overexpression also negatively correlated with FGFR3 protein expression (p = 0.021). We found that Rab23 expression was lower in normal bladder transitional cell line SV-HUC-1 than in bladder cancer cell lines BIU-87, 5637, and T24. We knocked down Rab23 expression in T24 cancer cells and transfected a Rab23 plasmid in the BIU-87 cell line. Rab23 depletion inhibited cell growth rate and invasion, while its overexpression resulted in increased cell growth and invasion. In addition, we demonstrated that Rab23 depletion decreased and its transfection upregulated expression of cyclin E, c-myc, and MMP-9. Furthermore, we showed that Rab23 knockdown inhibited NF-κB signaling and its overexpression upregulated NF-κB signaling. BAY 11-7082 (NF-κB inhibitor) partly inhibited the effect of Rab23 on cyclin E and MMP-9 expression. In conclusion, the present study demonstrated that Rab23 overexpression facilitates malignant cell growth and invasion in bladder cancer through the NF-κB pathway.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62(1):10–29.

    Article  PubMed  Google Scholar 

  2. Liang PY et al. Overexpression of immunoglobulin G prompts cell proliferation and inhibits cell apoptosis in human urothelial carcinoma. Tumour Biol. 2013;34(3):1783–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Castillo-Martin M et al. Molecular pathways of urothelial development and bladder tumorigenesis. Urol Oncol. 2010;28(4):401–8.

    Article  CAS  PubMed  Google Scholar 

  4. McConkey DJ et al. Molecular genetics of bladder cancer: emerging mechanisms of tumor initiation and progression. Urol Oncol. 2010;28(4):429–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Al Hussain TO, Akhtar M. Molecular basis of urinary bladder cancer. Adv Anat Pathol. 2013;20(1):53–60.

    Article  CAS  PubMed  Google Scholar 

  6. Sanchez-Carbayo M. Hypermethylation in bladder cancer: biological pathways and translational applications. Tumour Biol. 2012;33(2):347–61.

    Article  CAS  PubMed  Google Scholar 

  7. Shan GY et al. Overexpression of RIN1 associates with tumor grade and progression in patients of bladder urothelial carcinoma. Tumour Biol. 2012;33(3):847–55.

    Article  CAS  PubMed  Google Scholar 

  8. Atkins CD, Wrzesinski SH. Radiotherapy plus chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012;367(4):380. author reply 380-1.

    PubMed  Google Scholar 

  9. Smith AC et al. A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium. J Cell Biol. 2007;176(3):263–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Guo A et al. Open brain gene product Rab23: expression pattern in the adult mouse brain and functional characterization. J Neurosci Res. 2006;83(6):1118–27.

    Article  CAS  PubMed  Google Scholar 

  11. Liu YJ et al. Rab23 is a potential biological target for treating hepatocellular carcinoma. World J Gastroenterol. 2007;13(7):1010–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kim KR et al. Gene expression profiling using oligonucleotide microarray in atrophic gastritis and intestinal metaplasia. Korean J Gastroenterol. 2007;49(4):209–24.

    PubMed  Google Scholar 

  13. Hou Q et al. Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. Cancer Res. 2008;68(12):4623–30.

    Article  CAS  PubMed  Google Scholar 

  14. Ho JR et al. Deregulation of Rab and Rab effector genes in bladder cancer. PLoS One. 2012;7(6), e39469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sung JY et al. FGFR3 overexpression is prognostic of adverse outcome for muscle-invasive bladder carcinoma treated with adjuvant chemotherapy. Urol Oncol. 2014;32(1):49 e23–31.

    Article  CAS  Google Scholar 

  16. Sun HJ et al. Sublocalization of Rab23, a mediator of Sonic hedgehog signaling pathway, in hepatocellular carcinoma cell lines. Mol Med Rep. 2012;6(6):1276–80.

    CAS  PubMed  Google Scholar 

  17. Kim JK, Diehl JA. Nuclear cyclin D1: an oncogenic driver in human cancer. J Cell Physiol. 2009;220(2):292–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Knudsen KE et al. Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene. 2006;25(11):1620–8.

    Article  CAS  PubMed  Google Scholar 

  19. Juan G, Cordon-Cardo C. Intranuclear compartmentalization of cyclin E during the cell cycle: disruption of the nucleoplasm-nucleolar shuttling of cyclin E in bladder cancer. Cancer Res. 2001;61(3):1220–6.

    CAS  PubMed  Google Scholar 

  20. Gordan JD, Thompson CB, Simon MC. HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell. 2007;12(2):108–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mahdy E et al. Chromosome 8 numerical aberration and C-MYC copy number gain in bladder cancer are linked to stage and grade. Anticancer Res. 2001;21(5):3167–73.

    CAS  PubMed  Google Scholar 

  22. Schmitz-Drager BJ et al. C-myc in bladder cancer. Clinical findings and analysis of mechanism. Urol Res. 1997;25 Suppl 1:S45–9.

    Article  CAS  PubMed  Google Scholar 

  23. Sauter G et al. C-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization. Am J Pathol. 1995;146(5):1131–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Massari F et al. Prognostic value of beta-tubulin-3 and c-Myc in muscle invasive urothelial carcinoma of the bladder. PLoS One. 2015;10(6), e0127908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kumar B et al. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity. Cancer Res. 2010;70(2):832–41.

    Article  CAS  PubMed  Google Scholar 

  26. Fuller K et al. Rab23 regulates Nodal signaling in vertebrate left-right patterning independently of the Hedgehog pathway. Dev Biol. 2014;391(2):182–95.

    Article  CAS  PubMed  Google Scholar 

  27. Eggenschwiler JT et al. Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins. Dev Biol. 2006;290(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  28. Eggenschwiler JT, Espinoza E, Anderson KV. Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature. 2001;412(6843):194–8.

    Article  CAS  PubMed  Google Scholar 

  29. Lee SJ et al. Interleukin-28A triggers wound healing migration of bladder cancer cells via NF-kappaB-mediated MMP-9 expression inducing the MAPK pathway. Cell Signal. 2012;24(9):1734–42.

    Article  CAS  PubMed  Google Scholar 

  30. Kim JK et al. Up-regulation of Bfl-1/A1 via NF-kappaB activation in cisplatin-resistant human bladder cancer cell line. Cancer Lett. 2004;212(1):61–70.

    Article  CAS  PubMed  Google Scholar 

  31. Miao Z et al. CARMA3 is overexpressed in colon cancer and regulates NF-kappaB activity and cyclin D1 expression. Biochem Biophys Res Commun. 2012;425(4):781–7.

    Article  CAS  PubMed  Google Scholar 

  32. El-Kady A et al. Cyclin D1 inhibits whereas c-Myc enhances the cytotoxicity of cisplatin in mouse pancreatic cancer cells via regulation of several members of the NF-kappaB and Bcl-2 families. J Carcinog. 2011;10:24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Seo M et al. Inhibitory heterotrimeric GTP-binding proteins inhibit hydrogen peroxide-induced apoptosis by up-regulation of Bcl-2 via NF-kappaB in H1299 human lung cancer cells. Biochem Biophys Res Commun. 2009;381(2):153–8.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The study was supported by the Social Development Foundation of Liaoning Science and Technology Department (No. 2102225085).

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Authors and Affiliations

  1. Department of Urology, The First affiliated Hospital of China Medical University, Shenyang, 110001, China

    Yuanjun Jiang, Yushuang Han & Weiwei Zhi

  2. Department of Radiotherapy, The First affiliated Hospital of China Medical University, Shenyang, 110001, China

    Chaonan Sun, Chuyang Han, Ning Han & Qiao Qiao

Authors
  1. Yuanjun Jiang
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  2. Yushuang Han
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  3. Chaonan Sun
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  4. Chuyang Han
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  5. Ning Han
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  6. Weiwei Zhi
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  7. Qiao Qiao
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Corresponding author

Correspondence to Qiao Qiao.

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The study protocol was approved by the institutional review board of China Medical University.

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The author declared no coflicts of interest.

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Tumor specimens were obtained with informed consent.

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Jiang, Y., Han, Y., Sun, C. et al. Rab23 is overexpressed in human bladder cancer and promotes cancer cell proliferation and invasion. Tumor Biol. 37, 8131–8138 (2016). https://doi.org/10.1007/s13277-015-4590-9

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  • DOI: https://doi.org/10.1007/s13277-015-4590-9

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