A Decade of Global mRNA and miRNA Profiling of HPV-Positive Cell Lines and Clinical Specimens



Bogumil Kaczkowski1, Marya Morevati2, Maria Rossing3, 4, Finn Cilius3, Bodil Norrild*, 2
1 The Bioinformatics Centre, Department of Biology and Biomedical Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark
2 Institute of Cellular and Molecular Medicine, DNA Tumour Virus Laboratory, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
3 Centre for Genomic Medicine, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
4 Department of Clinical Biochemistry, Copenhagen University Hospital, Blegdamsvej 5, DK-2100 Copenhagen, Denmark


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© Kaczkowski et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Institute of Cellular and Molecular Medicine, DNA Tumour Virus Laboratory, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen, Denmark; Tel: +45-22262963; E-mail: bnorrild@sund.ku.dk


Abstract

For more than a decade, global gene expression profiling has been extensively used to elucidate the biology of human papillomaviruses (HPV) and their role in cervical- and head-and-neck cancers. Since 2008, the expression profiling of miRNAs has been reported in multiple HPV studies. Two major strategies have been employed in the gene and miRNA profiling studies: In the first approach, HPV positive tumors were compared to normal tissues or to HPV negative tumors. The second strategy relied on analysis of cell cultures transfected with single HPV oncogenes or with HPV genomes compared to untransfected cells considered as models for the development of premalignant and malignant transformations.

In this review, we summarize what we have learned from a decade of global expression profiling studies. We performed comprehensive analysis of the overlap of the lists of differentially expressed genes and microRNAs, in both tissue samples and cell culture based studies. The review focuses mainly on HPV16, however reports from other HPV species are used as references. We discuss the low degree of consensus among different studies and the limitation of differential expression analysis as well as the fragmented miRNA-mRNA target correlation evidence. Furthermore, we propose an approach for future research to include more comprehensive miRNA-mRNA target correlation analysis and to apply systems biology/gene networks methodology.

Keywords: Cervical cancer, head-and-neck cancer, HPV, messenger RNA profiling, miRNA..