Expression levels of miR-34-family microRNAs are associated with TP53 mutation status in head and neck squamous cell carcinoma
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.
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.
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.
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.
KeywordsHead and neck squamous cell carcinoma HNSCC MicroRNA MiR-34 TP53
This research project was supported by Siriraj Research Fund, Grant Number (IO) R015832023, Faculty of Medicine Siriraj Hospital, Mahidol University. The authors would like to thank Dr. Arathaya Thianboonsong and Dr. Wannaporn Deetipprasert for clinical assistance and Thitima Auekit for pathological assistance.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in the study. All procedures performed in this study involving human participants were in accordance with the ethical standards of the Declaration of Helsinki and approved by Siriraj Institutional Review Board (COA no. Si 424/2015).
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