Skip to main content

Advertisement

SpringerLink
Log in

The relevance of miRNAs as promising biomarkers in lip cancer

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

This study aimed to analyze the expression of miR-181b, miR-21, miR-31, and miR-345 in actinic cheilitis with and without epithelial dysplasia and lower lip squamous cell carcinomas, and to verify if the deregulated expression of these miRNAs would be indicative of malignant transformation.

Materials and methods

The sample was selected from formalin-fixed paraffin-embedded tissues of 19 actinic cheilitis without epithelial dysplasia, 32 actinic cheilitis with epithelial dysplasia, 42 lower lip squamous cell carcinomas, and 10 nonaltered oral mucosa of the lip. The microRNA (miR, miRNA) expression was quantified by real-time RT-PCR and the expression of the selected miRNAs among the groups of actinic cheilitis and lower lip cancer was compared by chi-square.

Results

A higher expression of miR-181b, miR-31, and miR-345 was found in actinic cheilitis without epithelial dysplasia in comparison to that in actinic cheilitis with epithelial dysplasia and with lower lip cancer. There were no differences in miR-21 expression between actinic cheilitis and lower lip cancer. Hierarchical clustering analysis showed a tendency for a downregulation of miR-181b, miR-21, miR-31, and miR-345 in most patients with lower lip cancers.

Conclusions

The upregulation of miR-181b, miR-31, and miR-345 expression in actinic cheilitis without epithelial dysplasia and the decrease in the expression of these miRNAs in actinic cheilitis with epithelial dysplasia and in lower lip cancer are potential biomarkers of malignant progression.

Clinical relevance

This miRNA signature can help to identify actinic cheilitis with potential to progress to lip cancer.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  1. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. https://doi.org/10.1016/j.cell.2009.01.002

    Article  PubMed  PubMed Central  Google Scholar 

  2. Courthod G, Franco P, Palermo L, Pisconti S, Numico G (2014) The role of microRNA in head and neck cancer: current knowledge and perspectives. Molecules 19(5):5704–5716. https://doi.org/10.3390/molecules19055704

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chattopadhyay E, De Sarkar N, Singh R, Ray A, Roy R, Paul RR, Pal M, Ghose S, Ghosh S, Kabiraj D, Banerjee R, Roy B (2016) Genome-wide mitochondrial DNA sequence variations and lower expression of OXPHOS genes predict mitochondrial dysfunction in oral cancer tissue. Tumour Biol 37(9):11861–11871. https://doi.org/10.1007/s13277-016-5026-x

    Article  PubMed  Google Scholar 

  4. Cao M, Zheng L, Liu J, Dobleman T, Hu S, Go VLW, Gao G, Xiao GG (2018) MicroRNAs as effective surrogate biomarkers for early diagnosis of oral cancer. Clin Oral Investig 22(2):571–581. https://doi.org/10.1007/s00784-017-2317-6

    Article  PubMed  Google Scholar 

  5. Min A, Zhu C, Peng S, Rajthala S, Costea DE, Sapkota D (2015) MicroRNAs as important players and biomarkers in oral carcinogenesis. Biomed Res Int 2015:186904. https://doi.org/10.1155/2015/186904

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ramassone A, Pagotto S, Veronese A, Visone R (2018) Epigenetics and MicroRNAs in cancer. Int J Mol Sci 19(2). https://doi.org/10.3390/ijms19020459

  7. Maclellan SA, Lawson J, Baik J, Guillaud M, Poh CF, Garnis C (2012) Differential expression of miRNAs in the serum of patients with high-risk oral lesions. Cancer Med 1(2):268–274. https://doi.org/10.1002/cam4.17

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhang H, Li T, Zheng L, Huang X (2017) Biomarker MicroRNAs for diagnosis of oral squamous cell carcinoma identified based on gene expression data and MicroRNA-mRNA network analysis. Comput Math Methods Med 2017:9803018. https://doi.org/10.1155/2017/9803018

    Article  PubMed  PubMed Central  Google Scholar 

  9. Troiano G, Mastrangelo F, Caponio VCA, Laino L, Cirillo N, Lo Muzio L (2018) Predictive prognostic value of tissue-based microRNA expression in oral squamous cell carcinoma: a systematic review and meta-analysis. J Dent Res 97(7):759–766. https://doi.org/10.1177/0022034518762090

    Article  PubMed  Google Scholar 

  10. Liu CJ, Kao SY, Tu HF, Tsai MM, Chang KW, Lin SC (2010) Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis 16(4):360–364. https://doi.org/10.1111/j.1601-0825.2009.01646.x

    Article  PubMed  Google Scholar 

  11. El-Sakka H, Kujan O, Farah CS (2018) Assessing miRNAs profile expression as a risk stratification biomarker in oral potentially malignant disorders: a systematic review. Oral Oncol 77:57–82. https://doi.org/10.1016/j.oraloncology.2017.11.021

    Article  PubMed  Google Scholar 

  12. Gale NP, Sidransky D, Westra W, Califano J (2005) Epithelial precursor lesions. In: Barnes L, Eveson JW, Reichart P, Sidransky D, et al. (eds). In: Press I (ed) World Health Organization Classification of Tumours. Pathology and Genetics. Head and Neck Tumours. Lyon, France, pp 140–143

  13. Reibel J, Gale N, Hille J, Hunt JL, Lingen M, Muller S et al (2017) Oral potentially malignant disorders and oral epithelial dysplasia. In: ElNaggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO Classification of head and neck tumours, 4th edn. International Agency for Research on Cancer, Lyon, pp 112–115

    Google Scholar 

  14. Speight PM, Abram TJ, Floriano PN et al (2015) Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials. Oral Surg Oral Med Oral Pathol Oral Radiol 120(4):474–482. https://doi.org/10.1016/j.oooo.2015.05.023

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nagata G, Santana T, Queiroz A, Caramez RH, Trierveiler M (2018) Evaluation of epithelial dysplasia adjacent to lip squamous cell carcinoma indicates that the degree of dysplasia is not associated with the occurrence of invasive carcinoma in this site. J Cutan Pathol. https://doi.org/10.1111/cup.13270

  16. Pilati S, Bianco BC, Vieira D, Modolo F (2017) Histopathologic features in actinic cheilitis by the comparison of grading dysplasia systems. Oral Dis 23(2):219–224. https://doi.org/10.1111/odi.12597

    Article  PubMed  Google Scholar 

  17. Cervigne NK, Reis PP, Machado J, Sadikovic B, Bradley G, Galloni NN, Pintilie M, Jurisica I, Perez-Ordonez B, Gilbert R, Gullane P, Irish J, Kamel-Reid S (2009) Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Hum Mol Genet 18(24):4818–4829. https://doi.org/10.1093/hmg/ddp446

    Article  PubMed  Google Scholar 

  18. Xiao W, Bao ZX, Zhang CY, Zhang XY, Shi LJ, Zhou ZT, Jiang WW (2012) Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia. PLoS One 7(6):e38648. https://doi.org/10.1371/journal.pone.0038648

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yang Y, Li YX, Yang X, Jiang L, Zhou ZJ, Zhu YQ (2013) Progress risk assessment of oral premalignant lesions with saliva miRNA analysis. BMC Cancer 13:129. https://doi.org/10.1186/1471-2407-13-129

    Article  PubMed  PubMed Central  Google Scholar 

  20. Brito JA, Gomes CC, Guimaraes AL, Campos K, Gomez RS (2014) Relationship between microRNA expression levels and histopathological features of dysplasia in oral leukoplakia. J Oral Pathol Med 43(3):211–216. https://doi.org/10.1111/jop.12112

    Article  PubMed  Google Scholar 

  21. Maimaiti A, Abudoukeremu K, Tie L, Pan Y, Li X (2015) MicroRNA expression profiling and functional annotation analysis of their targets associated with the malignant transformation of oral leukoplakia. Gene 558(2):271–277. https://doi.org/10.1016/j.gene.2015.01.004

    Article  PubMed  Google Scholar 

  22. Zhu G, He Y, Yang S, Chen B, Zhou M, Xu XJ (2015, 2015) Identification of gene and MicroRNA signatures for oral cancer developed from oral leukoplakia. Biomed Res Int:841956. https://doi.org/10.1155/2015/841956

  23. Hung KF, Liu CJ, Chiu PC, Lin JS, Chang KW, Shih WY, Kao SY, Tu HF (2016) MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder. Oral Oncol 53:42–47. https://doi.org/10.1016/j.oraloncology.2015.11.017

    Article  PubMed  Google Scholar 

  24. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262

    Article  PubMed  Google Scholar 

  25. Brito BL, Lourenco SV, Damascena AS, Kowalski LP, Soares FA, Coutinho-Camillo CM (2016) Expression of stem cell-regulating miRNAs in oral cavity and oropharynx squamous cell carcinoma. J Oral Pathol Med 45(9):647–654. https://doi.org/10.1111/jop.12424

    Article  PubMed  Google Scholar 

  26. Yang CC, Hung PS, Wang PW, Liu CJ, Chu TH, Cheng HW, Lin SC (2011) miR-181 as a putative biomarker for lymph-node metastasis of oral squamous cell carcinoma. J Oral Pathol Med 40(5):397–404. https://doi.org/10.1111/j.1600-0714.2010.01003.x

    Article  PubMed  Google Scholar 

  27. Deng ZY, Wang YH, Quan HZ, Liu OS, Li YP, Li Y, Zhu W, Munnee K, Tang ZG (2016) Investigation of the association between miR181b, Bcl2 and LRIG1 in oral verrucous carcinoma. Mol Med Rep 14(4):2991–2996. https://doi.org/10.3892/mmr.2016.5608

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yin J, Shi Z, Wei W, Lu C, Wei Y, Yan W, Li R, Zhang J, You Y, Wang X (2020) MiR-181b suppress glioblastoma multiforme growth through inhibition of SP1-mediated glucose metabolism. Cancer Cell Int 20:69. https://doi.org/10.1186/s12935-020-1149-7

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lin Z, Li D, Cheng W, Wu J, Wang K, Hu Y (2019) MicroRNA-181 Functions as an antioncogene and mediates NF-kappaB pathway by targeting RTKN2 in ovarian cancers. Reprod Sci 26(8):1071–1081. https://doi.org/10.1177/1933719118805865

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported Brazilian National Council for Scientific and Technological Development (CNPq) grant: #870891/1999-5 and partially supported by “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil- CAPES,” financial code #001.

Author information

Authors and Affiliations

  1. Department of Surgery, Stomatology, Pathology and Radiology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75, Bauru, São Paulo, 17012-901, Brazil

    Agnes Assao & Denise Tostes Oliveira

  2. Department of Histopathology, Botucatu Medical School, Paulista State University, São Paulo, Brazil

    Maria Aparecida Custódio Domingues & Eliana Maria Minicucci

  3. International Research Center, A.C.Camargo Cancer Center, São Paulo, SP, Brazil

    Fabio Albuquerque Marchi & Cláudia Malheiros Coutinho-Camillo

Authors
  1. Agnes Assao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Aparecida Custódio Domingues
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eliana Maria Minicucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fabio Albuquerque Marchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cláudia Malheiros Coutinho-Camillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Denise Tostes Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Denise Tostes Oliveira.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Committee of Ethics and Research of the Bauru School of Dentistry, University of São Paulo, has approved this study (process #: 1.929.331 – CAAE 63879016.5.0000.5417).

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

Assao, A., Domingues, M.A.C., Minicucci, E.M. et al. The relevance of miRNAs as promising biomarkers in lip cancer. Clin Oral Invest 25, 4591–4598 (2021). https://doi.org/10.1007/s00784-020-03773-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-020-03773-9

Keywords

Search

Navigation