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Molecular Cancer
Published in: Molecular Cancer 1/2015

Open Access 01-12-2015 | Research

Alcohol-dysregulated miR-30a and miR-934 in head and neck squamous cell carcinoma

Authors: Maarouf A. Saad, Selena Z. Kuo, Elham Rahimy, Angela E. Zou, Avinaash Korrapati, Mehran Rahimy, Elizabeth Kim, Hao Zheng, Michael Andrew Yu, Jessica Wang-Rodriguez, Weg M. Ongkeko

Published in: Molecular Cancer | Issue 1/2015

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Abstract

Background

Alcohol consumption is a well-established risk factor for head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanisms by which alcohol promotes HNSCC pathogenesis and progression remain poorly understood. Our study sought to identify microRNAs that are dysregulated in alcohol-associated HNSCC and investigate their contribution to the malignant phenotype.

Method

Using RNA-sequencing data from 136 HNSCC patients, we compared the expression levels of 1,046 microRNAs between drinking and non-drinking cohorts. Dysregulated microRNAs were verified by qRT-PCR in normal oral keratinocytes treated with biologically relevant doses of ethanol and acetaldehyde. The most promising microRNA candidates were investigated for their effects on cellular proliferation and invasion, sensitivity to cisplatin, and expression of cancer stem cell genes. Finally, putative target genes were identified and evaluated in vitro to further establish roles for these miRNAs in alcohol-associated HNSCC.

Results

From RNA-sequencing analysis we identified 8 miRNAs to be significantly upregulated in alcohol-associated HNSCCs. qRT-PCR experiments determined that among these candidates, miR-30a and miR-934 were the most highly upregulated in vitro by alcohol and acetaldehyde. Overexpression of miR-30a and miR-934 in normal and HNSCC cell lines produced up to a 2-fold increase in cellular proliferation, as well as induction of the anti-apoptotic gene BCL-2. Upon inhibition of these miRNAs, HNSCC cell lines exhibited increased sensitivity to cisplatin and reduced matrigel invasion. miRNA knockdown also indicated direct targeting of several tumor suppressor genes by miR-30a and miR-934.

Conclusions

Alcohol induces the dysregulation of miR-30a and miR-934, which may play crucial roles in HNSCC pathogenesis and progression. Future investigation of the alcohol-mediated pathways effecting these transformations will prove valuable for furthering the understanding and treatment of alcohol-associated HNSCC.
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Metadata
Title
Alcohol-dysregulated miR-30a and miR-934 in head and neck squamous cell carcinoma
Authors
Maarouf A. Saad
Selena Z. Kuo
Elham Rahimy
Angela E. Zou
Avinaash Korrapati
Mehran Rahimy
Elizabeth Kim
Hao Zheng
Michael Andrew Yu
Jessica Wang-Rodriguez
Weg M. Ongkeko
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-015-0452-8

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