Expression levels of miR-34-family microRNAs are associated with TP53 mutation status in head and neck squamous cell carcinoma

Abstract

Purpose: The majority of head and neck squamous cell carcinoma (HNSCC) cases in developing countries are associated with cigarette smoking and TP53 mutations. p53 is a transcription factor that activates downstream genes, including the hsa-miR-34a and hsa-miR-34b/c loci, to achieve cell-cycle arrest, senescence, and/or apoptosis. This study examined the differences in expression levels of miR-34 in HNSCC with or without TP53 mutations. Methods: We examined surgically resected tumor samples and normal adjacent tissues from HNSCC in oral cavity, larynx, and hypopharynx for TP53 mutations (exons 5–8) and miR-34 expression levels. Results: miR-34a, miR-34b, miR-34b*, and miR-34c are significantly up-regulated in tumors with wild-type TP53 genes (n = 23); while such up-regulation is not observed in tumors with mutant TP53 (n = 19). Although expression levels of miR-34-family miRNAs do not correlate with gender, age, or tumor staging, interestingly they are correlated with smoking status and tumor sites. miR-34b/b*/c are up-regulated in tumors from those who ever smoked or recently smoked (quit smoking less than 15 years ago); but such up-regulation was not seen in those who never smoked or quit smoking for at least 15 years. HNSCC of the oral cavity also up-regulated miR-34b/b*/c while no such overexpression was observed in HNSCC of the larynx and hypopharynx. Conclusions: Surgically resected HNSCC samples with no TP53 mutations have elevated levels of miR-34a and miR-34b/b*/c, while those with TP53 mutations show no such up-regulation. miR-34b/b*/c expression is also correlated with smoking status and tumor sites.