Comparison of the miRNA profiles in HPV-positive and HPV-negative tonsillar tumors and a model system of human keratinocyte clones

Abstract

BackgroundBetter 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. Here we aimed to characterize the expression profiles in a matched set of well-characterized HPV-dependent and HPV-independent tonsillar tumors and equivalent immortalized keratinocyte clones to define potential and clinically relevant biomarkers of HNC of different etiology.MethodsFresh frozen tonsillar cancer tissues were analyzed together with non-malignant tonsillar tissues and compared with cervical tumors and normal cervical tissues. Furthermore, relative miRNAs abundance levels of primary and immortalized human keratinocyte clones were evaluated. The global quantitation of miRNA gene abundance was performed using a TaqMan Low Density Array system. The confirmation of differentially expressed miRNAs was performed on a set of formalin-fixed paraffin-embedded tumor samples enriched for the tumor cell fraction by macrodissection.ResultsWe defined 46 upregulated and 31 downregulated miRNAs characteristic for the HPV-positive tonsillar tumors and 42 upregulated miRNAs and 42 downregulated miRNAs characteristic for HPV-independent tumors. In comparison with the expression profiles in cervical tumors, we defined miR-141-3p, miR-15b-5p, miR-200a-3p, miR-302c-3p, and miR-9-5p as specific for HPV induced malignancies. MiR-335-5p, miR-579-3p, and miR-126-5p were shared by the expression profiles of HPV-positive tonsillar tumors and of the HPV immortalized keratinocyte clones, whereas miR-328-3p, miR-34c-3p, and miR-885-5p were shared by the miRNA profiles of HPV-negative tonsillar tumors and the HPV-negative keratinocytes.ConclusionsWe identified the miRNAs characteristic for HPV-induced tumors and tonsillar tumors of different etiology, and the results were compared with those of the model system. Our report presents the basis for further investigations leading to the identification of clinically relevant diagnostic and/or therapeutic biomarkers for tumors of viral and non-viral etiology.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2430-y) contains supplementary material, which is available to authorized users.

Triage of high-risk HPV-positive women in population-based screening by miRNA expression analysis in cervical scrapes; a feasibility study

“…Overexpression of miR-15b-5p has previously been associated with HPV-induced malignancies including cervical cancer, tonsillar tumors, and anal carcinomas [ 40 , 41 ]. Moreover, miR-15b-5p was shown to promote cell viability, migration, and invasion in non-small cell lung cancer by targeting metastasis suppressor TIMP2 [ 42 ].…”

HPV epigenetic mechanisms related to Oropharyngeal and Cervix cancers

“…High-risk HPV infection leads to aberrant expression of cellular oncogenic and tumor suppressive miRNAs. 47 Many researchers have focused on the occurrence of epigenetic phenomena in OSCC development 48 Epigenetic changes represent an important mechanism for the silencing of tumor suppressor genes. 49 Further miRNA genes are subject to epigenetic changes.…”

Smoking-induced control of miR-133a-3p alters the expression of EGFR and HuR in HPV-infected oropharyngeal cancer

“…Furthermore, miR-133a-3p has been noted as a tumor suppressor miRNA downregulated in several cancers including HNSCC tumors and also known to target EGFR [ 31 – 34 ]. In bladder cancer downregulated miR-133a-3p was reported to serve as a potential biomarker for bladder cancer progression [ 35 , 36 ].…”