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Down-regulation of miR-200c associates with poor prognosis of oral squamous cell carcinoma

International Journal of Clinical Oncology volume 25, pages 1072–1078 (2020)Cite this article

Abstract

Background

MicroRNAs (miRNAs) are considered as promising cancer biomarkers. The aim of the present study is to investigate the prognostic significance of miR-200c in patients with oral squamous cell carcinoma (OSCC).

Materials and methods

Quantitative real-time PCR (qRT-PCR) was used to determine the expression levels of miR-200c in 204 pairs of OSCC and adjacent noncancerous. Correlations between miR-200c expression levels and clinicopathological characteristics were investigated. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Multivariate analysis of the prognostic factors was performed with a Cox proportional hazards regression model.

Results

The expression of miR-200c was significantly down-regulated in OSCC tissues compared with adjacent non-tumor tissues (p < 0.0001). Low expression of miR-200c in tumor tissues was significantly correlated with the positive N classification (p = 0.013), advanced TNM stage (p = 0.007) and poor differentiation grade (p = 0.026). Lower miR-200c expression in patients was significantly associated with poor recurrence-free survival (RFS, p = 0.0003) and overall survival (OS, p = 0.0026). Multivariate analysis confirmed that low miR-200c expression was an independent predictor for poor RFS (hazard ratio (HR) 1.705, 95% CI 1.136–2.56, p = 0.01) and OS (HR 1.669, 95% CI 1.03–2.703, p = 0.037) in patients with OSCC.

Conclusion

Our results suggest that the miR-200c might be a potential prognostic biomarker for OSCC.

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References

  1. Zhao X, Sun S, Zeng X et al (2018) Expression profiles analysis identifies a novel three-mRNA signature to predict overall survival in oral squamous cell carcinoma. Am J Cancer Res 8(3):450–461

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Markopoulos AK (2012) Current aspects on oral squamous cell carcinoma. Open Dent J 6:126–130

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424

    Article  PubMed  Google Scholar 

  4. Singhvi HR, Malik A, Chaturvedi P (2017) The role of chronic mucosal trauma in oral cancer: a review of literature. Indian J Med Paediatr Oncol 38(1):44–50

    Article  PubMed  PubMed Central  Google Scholar 

  5. Scully C, Bagan J (2009) Oral squamous cell carcinoma overview. Oral Oncol 45(4–5):301–308

    CAS  Article  PubMed  Google Scholar 

  6. Woolgar JA, Hall GL (2009) Determinants of outcome following surgery for oral squamous cell carcinoma. Future Oncol 5(1):51–61

    Article  PubMed  Google Scholar 

  7. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Macfarlane LA, Murphy PR (2010) MicroRNA: biogenesis, function and role in cancer. Curr Genom 11(7):537–561

    CAS  Article  Google Scholar 

  9. Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10(10):704–714

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Irani S (2016) miRNAs signature in head and neck squamous cell carcinoma metastasis: a literature review. J Dent (Shiraz) 17(2):71–83

    Google Scholar 

  11. Jakob M, Mattes LM, Küffer S et al (2019) MicroRNA expression patterns in oral squamous cell carcinoma: hsa-mir-99b-3p and hsa-mir-100-5p as novel prognostic markers for oral cancer. Head Neck 41(10):3499–3515

    Article  PubMed  Google Scholar 

  12. Shi J, Bao X, Liu Z et al (2019) Serum miR-626 and miR-5100 are promising prognosis predictors for oral squamous cell carcinoma. Theranostics 9(4):920–931

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Baba O, Hasegawa S, Nagai H et al (2016) MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis. J Oral Pathol Med 45(4):248–255

    CAS  Article  PubMed  Google Scholar 

  14. Park SM, Gaur AB, Lengyel E et al (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22(7):894–907

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Wong CM, Wei L, Au SL et al (2015) MiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis. Oncotarget 6(15):13658–13670

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zhang JY, Wang YM, Song LB et al (2016) Prognostic significance of microRNA-200c in various types of cancer: an updated meta-analysis of 34 studies. Mol Clin Oncol 4(6):933–941

    Article  PubMed  PubMed Central  Google Scholar 

  17. Patel S, Shah K, Mirza S et al (2015) Epigenetic regulators governing cancer stem cells and epithelial-mesenchymal transition in oral squamous cell carcinoma. Curr Stem Cell Res Ther 10(2):140–152

    CAS  Article  PubMed  Google Scholar 

  18. Kawakubo-Yasukochi T, Morioka M, Hazekawa M et al (2018) miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment. Mol Carcinog 57(2):295–302

    CAS  Article  PubMed  Google Scholar 

  19. Xie NN, Liu ZX, Wu C et al (2018) MicroRNA-200c suppresses tumor metastasis in oral squamous carcinoma by inhibiting epithelial-mesenchymal transition. Eur Rev Med Pharmacol Sci 22(11):3415–3422

    PubMed  Google Scholar 

  20. Yan Y, Yan F, Huang Q (2018) MiR-200c inhibited the proliferation of oral squamous cell carcinoma cells by targeting Akt pathway and its downstream Glut1. Arch Oral Biol 96:52–57

    CAS  Article  PubMed  Google Scholar 

  21. Chen W, Zheng R, Baade PD et al (2016) Cancer statistics in China, (2016). CA Cancer J Clin 66(2):115–132

    Article  PubMed  Google Scholar 

  22. Argiris A, Karamouzis MV, Raben D et al (2008) Head and neck cancer. Lancet 371(9625):1695–1709

    CAS  Article  PubMed  Google Scholar 

  23. Hayes J, Peruzzi PP, Lawler S (2014) MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med 20(8):460–469

    CAS  Article  PubMed  Google Scholar 

  24. Jamali Z, Asl Aminabadi N, Attaran R et al (2015) MicroRNAs as prognostic molecular signatures in human head and neck squamous cell carcinoma: a systematic review and meta-analysis. Oral Oncol 51(4):321–331

    CAS  Article  PubMed  Google Scholar 

  25. Arunkumar G, Deva Magendhra Rao AK, Manikandan M et al (2018) Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma. Oncol Lett 15(1):649–657

    PubMed  Google Scholar 

  26. Chang CJ, Chao CH, Xia W et al (2011) p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13(3):317–323

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Tamura M, Sasaki Y, Kobashi K et al (2015) CRKL oncogene is downregulated by p53 through miR-200s. Cancer Sci 106(8):1033–1040

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Kim H, Yang JM, Ahn SH et al (2018) Potential oncogenic role and prognostic implication of microRNA-155-5p in oral squamous cell carcinoma. Anticancer Res 38(9):5193–5200

    CAS  Article  PubMed  Google Scholar 

  29. Wei D, Wang W, Shen B et al (2019) MicroRNA-199a-5p suppresses migration and invasion in oral squamous cell carcinoma through inhibiting the EMT-related transcription factor SOX4. Int J Mol Med 44(1):185–195

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Warnakulasuriya S (2020) Oral potentially malignant disorders: a comprehensive review on clinical aspects and management. Oral Oncol 102:104550

    Article  PubMed  Google Scholar 

  31. Mutlu M, Raza U, Saatci Ö et al (2016) miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance. J Mol Med (Berl) 94(6):629–644

    CAS  Article  Google Scholar 

  32. Armand-Labit V, Pradines A (2017) Circulating cell-free microRNAs as clinical cancer biomarkers. Biomol Concepts 8(2):61–81

    CAS  Article  PubMed  Google Scholar 

  33. Jarry J, Schadendorf D, Greenwood C et al (2014) The validity of circulating microRNAs in oncology: five years of challenges and contradictions. Mol Oncol 8(4):819–829

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank all the participants for their cooperation in this study.

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Affiliations

  1. State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610000, China

    Jian Song, Nian Zhang, Lideng Cao, Xingchen Ye, En Luo & Zhuang Zhang

  2. Department of Stomatology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116000, China

    Di Xiao

Authors
  1. Jian Song
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  2. Nian Zhang
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  3. Lideng Cao
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  4. Di Xiao
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  5. Xingchen Ye
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  6. En Luo
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  7. Zhuang Zhang
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Corresponding author

Correspondence to Zhuang Zhang.

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The authors declare that there is no conflict of interest.

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This study was approved by the ethics committee of West China Hospital.

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Written informed consent was obtained from all participants.

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Song, J., Zhang, N., Cao, L. et al. Down-regulation of miR-200c associates with poor prognosis of oral squamous cell carcinoma. Int J Clin Oncol 25, 1072–1078 (2020). https://doi.org/10.1007/s10147-020-01649-2

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  • DOI: https://doi.org/10.1007/s10147-020-01649-2

Keywords

  • Prognosis
  • Overall survival
  • Recurrence-free survival
  • microRNA-200c
  • Oral squamous cell carcinoma