Skip to main content

Advertisement

Log in

MCM5 promotes tumour proliferation and correlates with the progression and prognosis of renal cell carcinoma

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

To investigate the role of Minichromosome maintenance protein 5 (MCM5) in the clinical prognosis and biological function of renal cell carcinoma (RCC).

Methods

The Oncomine database was analysed to determine the differential expression of MCMs in RCC. A total of 50 RCC tissues were evaluated by immunohistochemistry (IHC), and the association between MCM5 and clinicopathologic features was determined. Kaplan–Meier curves and the log-rank test were applied for survival analysis. MCM5 expression in RCC tissues and cell lines was examined further by Western blotting. To explore the biological function of MCM5 in RCC, RCC cell lines (786-0, 769p) were transfected with shRNA-MCM5 or MCM5. Cell proliferation was assessed using MTT and colony-formation assays. Tumour xenografts were generated in nude mice to confirm the effects of MCM5 on tumour growth.

Results

MCM5 was significantly overexpressed in RCC tissues; this outcome was confirmed by the Oncomine database, IHC and Western blotting. IHC and LinkedOmics analysis demonstrated that the MCM5 expression was significantly associated with pathological stage, lymph node status, distant metastasis, and TNM stage (p < 0.05) but not with sex, age, position, or tumour size (p > 0.05). Furthermore, high MCM5 levels correlated with unfavourable clinical outcomes in RCC (p < 0.05). Additionally, MCM5 silencing inhibited RCC cell line proliferation and reduced 786-0 xenograft tumour growth; in contrast, MCM5 upregulation promoted cell proliferation.

Conclusion

MCM5 overexpression is associated with malignant status and poor prognosis in RCC. Additionally, MCM5 plays an important role in proliferation and may be a potential prognostic marker and novel therapeutic target for RCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30

    Article  PubMed  Google Scholar 

  2. Bhatt JR, Finelli A (2014) Landmarks in the diagnosis and treatment of renal cell carcinoma. Nat Rev Urol 11:517–525

    Article  PubMed  Google Scholar 

  3. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30

    Article  PubMed  Google Scholar 

  4. Jonasch E, Gao J, Rathmell WK (2014) Renal cell carcinoma. BMJ 349:g4797

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chen D, Zhu M, Su H et al (2018) LINC00961 restrains cancer progression via modulating epithelial-mesenchymal transition in renal cell carcinoma. J Cell Physiol 234(5):7257–7265

    Article  CAS  PubMed  Google Scholar 

  6. Li P, Wong YN, Armstrong K et al (2016) Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras. Cancer Med 5:169–181

    Article  PubMed  Google Scholar 

  7. Tye BK (1999) MCM proteins in DNA replication. Annu Rev Biochem 68:649–686

    Article  CAS  PubMed  Google Scholar 

  8. Giaginis C, Georgiadou M, Dimakopoulou K et al (2009) Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity. Dig Dis Sci 54:282–291

    Article  CAS  PubMed  Google Scholar 

  9. Giaginis C, Vgenopoulou S, Vielh P et al (2010) MCM proteins as diagnostic and prognostic tumor markers in the clinical setting. Histol Histopathol 25:351–370

    CAS  PubMed  Google Scholar 

  10. Gou K, Liu J, Feng X et al (2018) Expression of minichromosome maintenance proteins (MCM) and cancer prognosis: a meta-analysis. J Cancer 9:1518–1526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yu SY, Wang YP, Chang JY et al (2014) Increased expression of MCM5 is significantly associated with aggressive progression and poor prognosis of oral squamous cell carcinoma. J Oral Pathol Med 43:344–349

    Article  CAS  PubMed  Google Scholar 

  12. Liu YZ, Wang BS, Jiang YY et al (2017) MCMs expression in lung cancer: implication of prognostic significance. J Cancer 8:3641–3647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Giaginis C, Giagini A, Tsourouflis G et al (2011) MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and comparison with Ki-67 proliferative marker. Dig Dis Sci 56:777–785

    Article  CAS  PubMed  Google Scholar 

  14. Wang D, Li Q, Li Y et al (2018) The role of MCM5 expression in cervical cancer: Correlation with progression and prognosis. Biomed Pharmacother 98:165–172

    Article  CAS  PubMed  Google Scholar 

  15. Kelly JD, Dudderidge TJ, Wollenschlaeger A et al (2012) Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of Mcm5 and nuclear matrix protein 22. PLoS ONE 7:e40305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rodins K, Cheale M, Coleman N et al (2002) Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential clinical utility. Clin Cancer Res 8:1075–1081

    CAS  PubMed  Google Scholar 

  17. Donaldson AD, Blow JJ (1999) The regulation of replication origin activation. Curr Opin Genet Dev 9:62–68

    Article  CAS  PubMed  Google Scholar 

  18. Bell SP, Dutta A (2002) DNA replication in eukaryotic cells. Annu Rev Biochem 71:333–374

    Article  CAS  PubMed  Google Scholar 

  19. Zhong H, Chen B, Neves H et al (2017) Expression of minichromosome maintenance genes in renal cell carcinoma. Cancer Manag Res 9:637–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mehdi MZ, Nagi AH, Naseem N (2016) MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: a quantitative and semi-quantitative analysis. Int Braz J Urol 42:1121–1128

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kanu N, Gronroos E, Martinez P et al (2015) SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair. Oncogene 34:5699–5708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Murphy N, Ring M, Heffron CC et al (2005) Quantitation of CDC6 and MCM5 mRNA in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix. Mod Pathol 18:844–849

    Article  CAS  PubMed  Google Scholar 

  23. Burger M (2009) MCM2 and MCM5 as prognostic markers in colon cancer: a worthwhile approach. Dig Dis Sci 54:197–198

    Article  PubMed  Google Scholar 

  24. Eissa S, Matboli M, Shehata HH et al (2015) MicroRNA-10b and minichromosome maintenance complex component 5 gene as prognostic biomarkers in breast cancer. Tumour Biol 36:4487–4494

    Article  CAS  PubMed  Google Scholar 

  25. Brems-Eskildsen AS, Zieger K, Toldbod H et al (2010) Prediction and diagnosis of bladder cancer recurrence based on urinary content of hTERT, SENP1, PPP1CA, and MCM5 transcripts. BMC Cancer 10:646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liao X, Han C, Wang X et al (2018) Prognostic value of minichromosome maintenance mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy. Cancer Manag Res 10:3255–3271

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Wang D, Zhu H, Guo M (2018) Expression and prognostic value of cell-cycle-associated genes in gastric adenocarcinoma. BMC Gastroenterol 18:81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Williams GH, Swinn R, Prevost AT et al (2004) Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates. Br J Cancer 91:714–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Keane MG, Huggett MT, Chapman MH et al (2017) Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in biliary brush cytology. Br J Cancer 116:349–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Dudderidge TJ, Kelly JD, Wollenschlaeger A et al (2010) Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments. Br J Cancer 103:701–707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Remus D, Beuron F, Tolun G et al (2009) Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell 139:719–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Su Z, Zheng X, Zhang X et al (2017) Sox10 regulates skin melanocyte proliferation by activating the DNA replication licensing factor MCM5. J Dermatol Sci 85:216–225

    Article  CAS  PubMed  Google Scholar 

  33. Agarwal MK, Ruhul Amin AR, Agarwal ML (2007) DNA replication licensing factor minichromosome maintenance deficient 5 rescues p53-mediated growth arrest. Cancer Res 67:116–121

    Article  CAS  PubMed  Google Scholar 

  34. Gakiopoulou H, Korkolopoulou P, Levidou G et al (2007) Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications. Br J Cancer 97:1124–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mio C, Lavarone E, Conzatti K et al (2016) MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer 23:335–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hsu I, Chuang KL, Slavin S et al (2014) Suppression of ERbeta signaling via ERbeta knockout or antagonist protects against bladder cancer development. Carcinogenesis 35:651–661

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study is supported by National Natural Science Foundation of China (NSFC) [81460137].

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yanping Luo or Ting Sun.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University.

Informed consent

Informed consent was provided by all patients who provided clinical specimens.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gong, B., Ma, M., Yang, X. et al. MCM5 promotes tumour proliferation and correlates with the progression and prognosis of renal cell carcinoma. Int Urol Nephrol 51, 1517–1526 (2019). https://doi.org/10.1007/s11255-019-02169-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-019-02169-3

Keywords

Navigation