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14.06.2016 | Original Article - Cancer Research | Ausgabe 8/2016

Journal of Cancer Research and Clinical Oncology 8/2016

Human papillomavirus E6 and E7 oncoproteins affect the expression of cancer-related microRNAs: additional evidence in HPV-induced tumorigenesis

Journal of Cancer Research and Clinical Oncology > Ausgabe 8/2016
Maria Vincenza Chiantore, Giorgio Mangino, Marco Iuliano, Maria Simona Zangrillo, Ilaria De Lillis, Gabriele Vaccari, Rosita Accardi, Massimo Tommasino, Sandra Columba Cabezas, Maurizio Federico, Gianna Fiorucci, Giovanna Romeo
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Electronic supplementary material

The online version of this article (doi:10.​1007/​s00432-016-2189-1) contains supplementary material, which is available to authorized users.
Gianna Fiorucci and Giovanna Romeo have contributed equally to this study and are listed in alphabetical order.



Human papillomaviruses (HPVs) are the causative agents of cervical cancer and are also associated with other types of cancers. HPVs can modulate microRNAs (miRNAs) expressed by infected cells. The production of extracellular vesicles is deregulated in cancer, and their cargo delivered to the microenvironment can promote tumorigenesis. The involvement of HPV oncoproteins on miRNA expression in cells and exosomes was analyzed in keratinocytes transduced with E6 and E7 from mucosal HPV-16 or cutaneous HPV-38 (K16 and K38).


MiRNAs were investigated through the TaqMan Array Human MicroRNA Cards, followed by real-time RT-PCR assay for specific miRNAs. Selected miRNA targets were analyzed by Western blot and correlated to the HPV oncoproteins by specifically silencing E6 and E7 expression. Exosomes, isolated from K16 and K38 supernatants by differential centrifugations, were quantified through the vesicle-associated acetylcholinesterase activity.


MiRNAs deregulated in K16 and K38 cells were identified. HPV-16 and/or HPV-38 E6 and E7 single proteins can modify the expression of selected miRNAs involved in the tumorigenesis, in particular miR-18a, -19a, -34a and -590-5p. The analysis of the content of exosomes isolated from HPV-positive cells revealed the presence of E6 and E7 mRNAs and few miRNAs. MiR-222, a key miRNA deregulated in many cancers, was identified in exosomes from K16 cells.


HPV E6 and/or E7 oncoprotein expression can induce the deregulation of some miRNAs. Through the production and function of exosomes, HPV oncogenes as well as HPV-deregulated miRNAs can potentiate the virus oncogenic effects in the tumor cell microenvironment.

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Supplementary material 1 (TIFF 185 kb)
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