MicroRNAs targeting CDKN2A gene as a potential prognostic marker in head and neck squamous cell carcinoma.

Abstract

Epigenetic factors are known to markedly influence the functions of a gene by modification of transcripts, via methylation or acetylation and degradation of mRNA transcripts. The CDKN2A encodes cyclin-dependent kinase inhibitor 2A, a tumour suppressor protein. Genetic and epigenetic alterations in this gene have been demonstrated in several cancer types. The non-coding RNAs with a special emphasis on microRNAs have long been explored for their potential role in the epigenetic modification of gene expression. The present study aims to identify the microRNAs targeting CDKN2A gene transcripts and demonstrate their prognostic significance in head and neck squamous cell carcinoma (HNSCC). Computational approaches were employed to identify the microRNAs targeting CDKN2A. The gene and protein expression profile of CDKN2A was analyzed using UALCAN. A significant upregulation of CDKN2A was observed in the primary tumour tissues (p=<10^-12). Interestingly, the protein expression, although found to be statistically significant (p=0.0129) did not correlate well with the gene expression profile. The microRNAs targeting CDKN2A were further analyzed to identify the possible reason for the decrease in protein expression. Among the 44 microRNAs targeting CDKN2A gene transcripts, hsa-miR-3681-3p, hsa-miR-542-5p, hsa-miR-4519 were found to be upregulated and hsa-miR-134-5p was found to be downregulated with a significant association with survival status of HNSCC patients. The hsa-miR-542-5p was found to correlate well with the survival and hence can be considered as the key microRNA associated with HNSCC. However, further validation of this microRNA is warranted to confirm its role in the process of carcinogenesis.