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Published in: European Archives of Oto-Rhino-Laryngology 2/2019

01-02-2019 | Head & Neck

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

Authors: Chanatip Metheetrairut, Chanticha Chotigavanich, Kanchana Amornpichetkul, Phawin Keskool, Sunun Ongard, Choakchai Metheetrairut

Published in: European Archives of Oto-Rhino-Laryngology | Issue 2/2019

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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.
Literature
3.
17.
18.
20.
go back to reference Dufour A, Palermo G, Zellmeier E, Mellert G, Duchateau-Nguyen G, Schneider S, Benthaus T, Kakadia PM, Spiekermann K, Hiddemann W, Braess J, Truong S, Patten N, Wu L, Lohmann S, Dornan D, GuhaThakurta D, Yeh RF, Salogub G, Solal-Celigny P, Dmoszynska A, Robak T, Montillo M, Catalano J, Geisler CH, Weisser M, Bohlander SK (2013) Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients. Blood 121(18):3650–3657. https://doi.org/10.1182/blood-2012-10-458695 CrossRefPubMed Dufour A, Palermo G, Zellmeier E, Mellert G, Duchateau-Nguyen G, Schneider S, Benthaus T, Kakadia PM, Spiekermann K, Hiddemann W, Braess J, Truong S, Patten N, Wu L, Lohmann S, Dornan D, GuhaThakurta D, Yeh RF, Salogub G, Solal-Celigny P, Dmoszynska A, Robak T, Montillo M, Catalano J, Geisler CH, Weisser M, Bohlander SK (2013) Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients. Blood 121(18):3650–3657. https://​doi.​org/​10.​1182/​blood-2012-10-458695 CrossRefPubMed
23.
go back to reference Resnick RM, Cornelissen MT, Wright DK, Eichinger GH, Fox HS, ter Schegget J, Manos MM (1990) Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst 82(18):1477–1484CrossRefPubMed Resnick RM, Cornelissen MT, Wright DK, Eichinger GH, Fox HS, ter Schegget J, Manos MM (1990) Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst 82(18):1477–1484CrossRefPubMed
26.
go back to reference de Anta JM, Jassem E, Rosell R, Martinez-Roca M, Jassem J, Martinez-Lopez E, Monzo M, Sanchez-Hernandez JJ, Moreno I, Sanchez-Cespedes M (1997) TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis. Oncogene 15(24):2951–2958. https://doi.org/10.1038/sj.onc.1201475 CrossRefPubMed de Anta JM, Jassem E, Rosell R, Martinez-Roca M, Jassem J, Martinez-Lopez E, Monzo M, Sanchez-Hernandez JJ, Moreno I, Sanchez-Cespedes M (1997) TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis. Oncogene 15(24):2951–2958. https://​doi.​org/​10.​1038/​sj.​onc.​1201475 CrossRefPubMed
29.
go back to reference Boonyaphiphat P, Pruegsanusak K, Thongsuksai P (2012) The prognostic value of p53, Bcl-2 and Bax expression in laryngeal cancer. J Med Assoc Thai 95(10):1317–1320PubMed Boonyaphiphat P, Pruegsanusak K, Thongsuksai P (2012) The prognostic value of p53, Bcl-2 and Bax expression in laryngeal cancer. J Med Assoc Thai 95(10):1317–1320PubMed
34.
go back to reference Rentoft M, Fahlen J, Coates PJ, Laurell G, Sjostrom B, Ryden P, Nylander K (2011) miRNA analysis of formalin-fixed squamous cell carcinomas of the tongue is affected by age of the samples. Int J Oncol 38(1):61–69PubMed Rentoft M, Fahlen J, Coates PJ, Laurell G, Sjostrom B, Ryden P, Nylander K (2011) miRNA analysis of formalin-fixed squamous cell carcinomas of the tongue is affected by age of the samples. Int J Oncol 38(1):61–69PubMed
37.
Metadata
Title
Expression levels of miR-34-family microRNAs are associated with TP53 mutation status in head and neck squamous cell carcinoma
Authors
Chanatip Metheetrairut
Chanticha Chotigavanich
Kanchana Amornpichetkul
Phawin Keskool
Sunun Ongard
Choakchai Metheetrairut
Publication date
01-02-2019
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Oto-Rhino-Laryngology / Issue 2/2019
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-018-5223-x

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