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

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.