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Association of MAPK and its regulatory miRNAs (603, 4301, 8485, and 4731) with the malignant transformation of oral lichen planus

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Abstract

Oral lichen planus (OLP) is a potentially malignant oral lesion that may transform into oral squamous cell carcinoma (OSCC). The purpose of this study was to assess the level of expression of MAPK/ERK1/2 gene, and microRNA (miR)-603, 4301, 8485, and 4731 in the MAPK signaling pathway in OLP and OSCC lesions. This case–control study evaluated 26 OSCC, 20 OLP and 20 healthy control tissue specimens. After RNA extraction, the respective miRNA and MAPK/ERK1/2 mRNA levels were assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR). Significant upregulation of MAPK/ERK1/2 gene was noted in the OLP and OSCC specimens compared with healthy controls (p < 0.001). The expression level of miR-4731 was significantly lower in the OLP and OSCC specimens than in the healthy specimens (p < 0.001). The expression of MiR-603 was the lowest in OLP, followed by OSCC and then the control group (p < 0.001). No significant difference was found in miR-4801 levels between OSCC and OLP specimens compared with healthy controls (p = 0.43 and p = 0.86, respectively). In addition, a non-significant decrease in miR-8485 levels was noted in the OSCC and OLP specimens compared with healthy controls (p = 0.98 and p = 0.61, respectively). A significant decrease in level of miR-603 was noted in OLP compared with OSCC group (p < 0.001). The miR-4801 and miR-8485 expression levels were directly correlated with MAPK/ERK1/2 mRNA expression (p = 0.01). Higher expression level of MAPK/ERK1/2, miR-603, miR-4801, and miR-4731, and lower expression level of miR-8485 were correlated with significantly lower overall survival rate in OSCC patients. The increased expression of MAPK/ERK1/2 and decreased expression of miR-603 and miR-4731 are associated with greater risk of OLP malignant transformation and poor histopathological characteristics of OSCC.

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Correspondence to Nafiseh Sheykhbahaei.

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Gholizadeh, N., Emami Razavi, A., Mohammadpour, H. et al. Association of MAPK and its regulatory miRNAs (603, 4301, 8485, and 4731) with the malignant transformation of oral lichen planus. Mol Biol Rep 47, 1223–1232 (2020) doi:10.1007/s11033-019-05223-6

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Keywords

  • MAPK/ERK1/2
  • miR-603
  • miR-4801
  • miR-8485
  • miR-4731
  • Oral lichen planus
  • Oral squamous cell carcinoma