engleski

Comparison of the miRNA profile in HPV positive and negative tonsillar tumors and HPV-immortalized human keratinocyte clones

Introduction: Better insights into the molecular changes involved in virus-associated and -independent head and neck cancer may advance our knowledge of HNC carcinogenesis and identify critical disease biomarkers. MicroRNAs are a class of noncoding small RNAs which are negative gene regulators. Their expression is deregulated in cancers and their abundance profiles are often specific for tumors of different origin. Aim: The aims of the study were to characterize the expression profiles of miRNAs in a matched set of HPV dependent and independent HNC and in isogenic primary human keratinocyte clones immortalized by HPV. Methods: Frozen tonsillar cancer tissues of HPV (N=13) and non-viral (N=10) etiology were analyzed together with the nonmalignant tonsillar tissue (N=5). Cervical tumors (N=5) and normal cervical tissues (N=2) were analyzed for comparison. Furthermore, expression profiles of 9 isogenic primary human foreskin keratinocytes clones were evaluated. The global quantitation of miRNA gene abundance was performed using the TaqMan® Low Density Array Human MicroRNA A+B Cards Set v3.0 (Life Technologies, USA) identifying a total of 754 miRNAs. Results: In the HPV positive tonsillar tissue and in the cervical cancer we have detected only two concordant differentially expressed miRNAs, suggestive of the specificity of the HPV induced malignancies. We have identified 30 miRNAs specific for tonsillar tumors and 9 miRNAs differentially expressed in all squamous cell carcinomas in comparison to theirs normal counterparts. Between HPV positive and negative tonsillar tumors, the levels of 9 miRNAs were increased and levels of 26 miRNAs were reduced. Analysis of miRNA expression profiles of human keratinocyte clones was conducted and the results compared to those of the analyzed tissues. Conclusions: The miRNAs exhibiting specific differential abundance patterns may reveal the new candidate genes and the cellular pathways targeted by HPV in the HNC development.

HPV; miRNA

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