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The upregulation of oncogenic miRNAs in swabbed samples obtained from oral premalignant and malignant lesions

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Abstract

Objectives

Oncogenic miRNAs upregulated in OSCC play a range of versatile roles in oral carcinogenesis. Oral potentially malignant disorders (OPMDs) are the antecedent lesions to oral squamous carcinoma (OSCC) and they require a definitive diagnosis and early intervention. This study hypothesizes the presence of aberrant oncogenic miRNA expression in swabbed oral lesions.

Materials and methods

The expression of miR-21, miR-31, miR-134, miR-146a, and miR-211 in swabbed samples from 36 dysplastic or hyperplastic OPMDs and 10 OSCCs, relative to respective normal mucosa within the same patient, is analyzed with qRT-PCR to develop a diagnosis.

Results

Upregulation of all tested miRNAs in OPMD and OSCC samples comparing to controls is found to have occurred. Receiver operating characteristics curve analysis shows that miR-31 gives the best diagnostic accuracy of 0.91 when differentiating OPMD/OSCC from controls. An analysis of miR-134 and miR-211 expression allows the discrimination of the dysplastic state associated with OPMD, while the use of expression of the combined miRNAs further improves the analytical performances when identifying the dysplastic state. The concordant upregulation of miR-21, miR-31, and miR-146a is found to occur during an early stage of OSCC carcinogenesis.

Conclusion

This study demonstrates the upregulation of multiple oncogenic miRNAs in swabbed OPMD and OSCC samples. miRNA expression in swabbed collectives enables the differentiation between normal mucosa and OPMD/OSCC, independent of their histopathological severity.

Clinical relevance

This conventional and convenient sampling tool, when coupled with an assessment of miR-31 expression, would seem to be an adjuvant approach to the diagnosis of OPMD and OSCC.

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References

  1. Chen YF, Yang CC, Kao SY, Liu CJ, Lin SC, Chang KW (2016) MicroRNA-211 enhances the oncogenicity of carcinogen-induced oral carcinoma by repressing TCF12 and increasing antioxidant activity. Cancer Res 76:4872–4886. https://doi.org/10.1158/0008-5472.CAN-15-1664

    Article  PubMed  Google Scholar 

  2. He Q, Chen Z, Cabay RJ, Zhang L, Luan X, Chen D, Yu T, Wang A, Zhou X (2016) microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection. Oral Oncol 57:15–20. https://doi.org/10.1016/j.oraloncology.2016.03.017

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, Perez-Ordonez B, Jurisica I, O’Sullivan B, Waldron J, Gullane P, Cummings B, Liu FF (2010) Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res 16:1129–1139. https://doi.org/10.1158/1078-0432.CCR-09-2166

    Article  PubMed  Google Scholar 

  4. Hung PS, Liu CJ, Chou CS, Kao SY, Yang CC, Chang KW, Chiu TH, Lin SC (2013) miR-146a enhances the oncogenicity of oral carcinoma by concomitant targeting of the IRAK1, TRAF6 and NUMB genes. PLoS ONE 8:e79926. https://doi.org/10.1371/journal.pone.0079926

    Article  PubMed  PubMed Central  Google Scholar 

  5. Liu CJ, Shen WG, Peng SY, Cheng HW, Kao SY, Lin SC, Chang KW (2014) miR-134 induces oncogenicity and metastasis in head and neck carcinoma through targeting WWOX gene. Int J Cancer 134:811–821. https://doi.org/10.1002/ijc.28358

    Article  PubMed  Google Scholar 

  6. Liu CJ, Tsai MM, Hung PS, Kao SY, Liu TY, Wu KJ, Chiou SH, Lin SC, Chang KW (2010) miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma. Cancer Res 70:1635–1644. https://doi.org/10.1158/0008-5472.CAN-09-2291

    Article  PubMed  Google Scholar 

  7. Chen M, Luo R, Li S, Li H, Qin Y, Zhou D, Liu H, Gong X, Chang J (2020) Paper-based strip for ultrasensitive detection of OSCC-associated salivary microRNA via CRISPR/Cas12a coupling with IS-primer amplification reaction. Anal Chem 92:13336–13342. https://doi.org/10.1021/acs.analchem.0c02642

    Article  PubMed  Google Scholar 

  8. Dumache R (2017) Early diagnosis of oral squamous cell carcinoma by salivary microRNAs. Clin Lab 63:1771–1776. https://doi.org/10.7754/Clin.Lab.2017.170607

    Article  PubMed  Google Scholar 

  9. He L, Ping F, Fan Z, Zhang C, Deng M, Cheng B, Xia J (2020) Salivary exosomal miR-24-3p serves as a potential detective biomarker for oral squamous cell carcinoma screening. Biomed Pharmacother 121:109553. https://doi.org/10.1016/j.biopha.2019.109553

    Article  PubMed  Google Scholar 

  10. Langevin S, Kuhnell D, Parry T, Biesiada J, Huang S, Wise-Draper T, Casper K, Zhang X, Medvedovic M, Kasper S (2017) Comprehensive microRNA-sequencing of exosomes derived from head and neck carcinoma cells in vitro reveals common secretion profiles and potential utility as salivary biomarkers. Oncotarget 8:82459–82474. https://doi.org/10.18632/oncotarget.19614

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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 16:360–364. https://doi.org/10.1111/j.1601-0825.2009.01646.x

    Article  PubMed  Google Scholar 

  12. Liu CJ, Lin SC, Yang CC, Cheng HW, Chang KW (2012) Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck 34:219–224. https://doi.org/10.1002/hed.21713

    Article  PubMed  Google Scholar 

  13. Manifar S, Koopaie M, Lahiji SS (2021) Assessment of microRNA-15a and microRNA-16-1 salivary level in oral squamous cell carcinoma patients. Microrna. https://doi.org/10.2174/2211536610666210506125036

    Article  PubMed  Google Scholar 

  14. Menini M, De Giovanni E, Bagnasco F, Delucchi F, Pera F, Baldi D, Pesce P (2021) Salivary micro-RNA and oral squamous cell carcinoma: a systematic review. J Pers Med 11:101. https://doi.org/10.3390/jpm11020101

  15. Liu CJ, Lin JS, Cheng HW, Hsu YH, Cheng CY, Lin SC (2017) Plasma miR-187* is a potential biomarker for oral carcinoma. Clin Oral Investig 21:1131–1138. https://doi.org/10.1007/s00784-016-1887-z

  16. Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, Poon TC, Ng SS, Sung JJ (2009) Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 58:1375–1381. https://doi.org/10.1136/gut.2008.167817

    Article  PubMed  Google Scholar 

  17. Pritzker KPH, Darling MR, Hwang JT, Mock D (2021) Oral potentially malignant disorders (OPMD): what is the clinical utility of dysplasia grade? Expert Rev Mol Diagn 21:289–298. https://doi.org/10.1080/14737159.2021.1898949

    Article  PubMed  Google Scholar 

  18. Chang KW, Lin SC, Kwan PC, Wong YK (2000) Association of aberrant p53 and p21(WAF1) immunoreactivity with the outcome of oral verrucous leukoplakia in Taiwan. J Oral Pathol Med 29:56–62. https://doi.org/10.1034/j.1600-0714.2000.290202.x

    Article  PubMed  Google Scholar 

  19. Lin SC, Liu CJ, Ko SY, Chang HC, Liu TY, Chang KW (2005) Copy number amplification of 3q26-27 oncogenes in microdissected oral squamous cell carcinoma and oral brushed samples from areca chewers. J Pathol 206:417–422. https://doi.org/10.1002/path.1790

    Article  PubMed  Google Scholar 

  20. Yang HW, Yu CC, Hsieh PL, Liao YW, Chu PM, Yu CH, Fang CY (2021) Arecoline enhances miR-21 to promote buccal mucosal fibroblasts activation. J Formos Med Assoc 120:1108–1113. https://doi.org/10.1016/j.jfma.2020.10.019

    Article  PubMed  Google Scholar 

  21. Dionne KR, Warnakulasuriya S, Zain RB, Cheong SC (2015) Potentially malignant disorders of the oral cavity: current practice and future directions in the clinic and laboratory. Int J Cancer 136:503–515. https://doi.org/10.1002/ijc.28754

    Article  PubMed  Google Scholar 

  22. Mello FW, Melo G, Guerra ENS, Warnakulasuriya S, Garnis C, Rivero ERC (2020) Oral potentially malignant disorders: a scoping review of prognostic biomarkers. Crit Rev Oncol Hematol 153:102986. https://doi.org/10.1016/j.critrevonc.2020.102986

    Article  PubMed  Google Scholar 

  23. Kuo TM, Luo SY, Chiang SL, Yeh KT, Hsu HT, Wu CT, Lu CY, Tsai MH, Chang JG, Ko YC (2015) Fibrotic effects of arecoline N-Oxide in oral potentially malignant disorders. J Agric Food Chem 63:5787–5794. https://doi.org/10.1021/acs.jafc.5b01351

    Article  PubMed  Google Scholar 

  24. Sathasivam HP, Kist R, Sloan P, Thomson P, Nugent M, Alexander J, Haider S, Robinson M (2021) Predicting the clinical outcome of oral potentially malignant disorders using transcriptomic-based molecular pathology. Br J Cancer. https://doi.org/10.1038/s41416-021-01411-z

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shieh TM, Lin SC, Liu CJ, Chang SS, Ku TH, Chang KW (2007) Association of expression aberrances and genetic polymorphisms of lysyl oxidase with areca-associated oral tumorigenesis. Clin Cancer Res 13:4378–4385. https://doi.org/10.1158/1078-0432.CCR-06-2685

    Article  PubMed  Google Scholar 

  26. 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 

  27. Hung PS, Tu HF, Kao SY, Yang CC, Liu CJ, Huang TY, Chang KW, Lin SC (2014) miR-31 is upregulated in oral premalignant epithelium and contributes to the immortalization of normal oral keratinocytes. Carcinogenesis 35:1162–1171. https://doi.org/10.1093/carcin/bgu024

    Article  PubMed  Google Scholar 

  28. Uma Maheswari TN, Nivedhitha MS, Ramani P (2020) Expression profile of salivary micro RNA-21 and 31 in oral potentially malignant disorders. Braz Oral Res 34:e002. https://doi.org/10.1590/1807-3107bor-2020.vol34.0002

    Article  PubMed  Google Scholar 

  29. Lin HP, Chen HM, Cheng SJ, Yu CH, Chiang CP (2012) Cryogun cryotherapy for oral leukoplakia. Head Neck 34:1306–1311. https://doi.org/10.1002/hed.21912

    Article  PubMed  Google Scholar 

  30. Wolfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Muller MA, Niemeyer D, Jones TC, Vollmar P, Rothe C, Hoelscher M, Bleicker T, Brunink S, Schneider J, Ehmann R, Zwirglmaier K, Drosten C, Wendtner C (2020) Virological assessment of hospitalized patients with COVID-2019. Nature 581:465–469. https://doi.org/10.1038/s41586-020-2196-x

    Article  PubMed  Google Scholar 

  31. Jovanovich S, Bogdan G, Belcinski R, Buscaino J, Burgi D, Butts ELR, Chear K, Ciopyk B, Eberhart D, El-Sissi O, Franklin H, Gangano S, Gass J, Harris D, Hennessy L, Kindwall A, King D, Klevenberg J, Li Y, Mehendale N, McIntosh R, Nielsen B, Park C, Pearson F, Schueren R, Stainton N, Troup C, Vallone PM, Vangbo M, Woudenberg T, Wyrick D, Williams S (2015) Developmental validation of a fully integrated sample-to-profile rapid human identification system for processing single-source reference buccal samples. Forensic Sci Int Genet 16:181–194. https://doi.org/10.1016/j.fsigen.2014.12.004

    Article  PubMed  Google Scholar 

  32. Cheng SJ, Chang CF, Ko HH, Liu YC, Peng HH, Wang HJ, Lin HS, Chiang CP (2017) Hypermethylated ZNF582 and PAX1 genes in oral scrapings collected from cancer-adjacent normal oral mucosal sites are associated with aggressive progression and poor prognosis of oral cancer. Oral Oncol 75:169–177. https://doi.org/10.1016/j.oraloncology.2017.11.013

    Article  PubMed  Google Scholar 

  33. Kujan O, Huang G, Ravindran A, Vijayan M, Farah CS (2019) CDK4, CDK6, cyclin D1 and Notch1 immunocytochemical expression of oral brush liquid-based cytology for the diagnosis of oral leukoplakia and oral cancer. J Oral Pathol Med 48:566–573. https://doi.org/10.1111/jop.12902

    Article  PubMed  Google Scholar 

  34. Zhou Y, Kolokythas A, Schwartz JL, Epstein JB, Adami GR (2017) microRNA from brush biopsy to characterize oral squamous cell carcinoma epithelium. Cancer Med 6:67–78. https://doi.org/10.1002/cam4.951

    Article  PubMed  Google Scholar 

  35. Lai YH, Liu H, Chiang WF, Chen TW, Chu LJ, Yu JS, Chen SJ, Chen HC, Tan BC (2018) MiR-31-5p-ACOX1 axis enhances tumorigenic fitness in oral squamous cell carcinoma via the promigratory prostaglandin E2. Theranostics 8:486–504. https://doi.org/10.7150/thno.22059

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wang X, Li GH (2018) MicroRNA-16 functions as a tumor-suppressor gene in oral squamous cell carcinoma by targeting AKT3 and BCL2L2. J Cell Physiol 233:9447–9457. https://doi.org/10.1002/jcp.26833

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kao YY, Tu HF, Kao SY, Chang KW, Lin SC (2015) The increase of oncogenic miRNA expression in tongue carcinogenesis of a mouse model. Oral Oncol 51:1103–1112. https://doi.org/10.1016/j.oraloncology.2015.10.007

    Article  PubMed  Google Scholar 

  38. Chang KW, Liu CJ, Chu TH, Cheng HW, Hung PS, Hu WY, Lin SC (2008) Association between high miR-211 microRNA expression and the poor prognosis of oral carcinoma. J Dent Res 87:1063–1068. https://doi.org/10.1177/154405910808701116

    Article  PubMed  Google Scholar 

  39. Chu TH, Yang CC, Liu CJ, Lui MT, Lin SC, Chang KW (2013) miR-211 promotes the progression of head and neck carcinomas by targeting TGFbetaRII. Cancer Lett 337:115–124. https://doi.org/10.1016/j.canlet.2013.05.032

    Article  PubMed  Google Scholar 

  40. Peng SY, Tu HF, Yang CC, Wu CH, Liu CJ, Chang KW, Lin SC (2018) miR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression. Int J Cancer 143:2892–2904. https://doi.org/10.1002/ijc.31638

    Article  PubMed  Google Scholar 

  41. Tu HF, Lin SC, Chang KW (2013) MicroRNA aberrances in head and neck cancer: pathogenetic and clinical significance. Curr Opin Otolaryngol Head Neck Surg 21:104–111. https://doi.org/10.1097/MOO.0b013e32835e1d6e

    Article  PubMed  Google Scholar 

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Acknowledgements

We acknowledge the help from Dr. Liu, Ko-Jiun and Dr. Shiah, Shine-Gwo.

Funding

This study is supported by grants 107–2314-B-010–032-MY3 from Ministry of Science and Technology and MOHW110-TDU-B-211–144019 from Ministry of Health and Welfare, Taiwan.

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Authors and Affiliations

  1. Institute of Oral Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Shu-Chun Lin, Si-Hua Ji, Wan-Wen Hung, Ying-Chieh Liu, Sih-Rou Chang, Hsi-Feng Tu & Kuo-Wei Chang

  2. Department of Dentistry, College of Dentistry, National Yang Ming Chiao Tung University, Li-Nong St, No 155, Beitou, Taipei, Taiwan, 11211

    Shu-Chun Lin, Chung-Ji Liu, Hsi-Feng Tu & Kuo-Wei Chang

  3. Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan

    Shu-Chun Lin & Kuo-Wei Chang

  4. Department of Dentistry, Taipei MacKay Memorial Hospital, Taipei, Taiwan

    Chung-Ji Liu

  5. Department of Dentistry, National Yang Ming Chiao Tung Hospital, Yi-Lan, Taiwan

    Hsi-Feng Tu

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  1. Shu-Chun Lin
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Correspondence to Kuo-Wei Chang.

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Lin, SC., Liu, CJ., Ji, SH. et al. The upregulation of oncogenic miRNAs in swabbed samples obtained from oral premalignant and malignant lesions. Clin Oral Invest 26, 1343–1351 (2022). https://doi.org/10.1007/s00784-021-04108-y

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  • DOI: https://doi.org/10.1007/s00784-021-04108-y

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