Journal
ONCOGENE
Volume 27, Issue 18, Pages 2575-2582Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210919
Keywords
HPVs; microRNA; cervical cancer; oncogene
Funding
- NIDCD NIH HHS [DC016406] Funding Source: Medline
- NIDCR NIH HHS [F31 DE019028-01A1, DE019028, F31 DE019028] Funding Source: Medline
- NIGMS NIH HHS [5T32GM065100, T32 GM065100] Funding Source: Medline
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Human papillomaviruses (HPVs) are involved in the pathogenesis of cancer of the cervix (CaCx). MicroRNA (miRNA) expression analysis using Ambion (Austin, TX, USA) arrays showed that three miRNAs were over-expressed and 24 underexpressed in cervical cell lines containing integrated HPV-16 DNA compared to the normal cervix. Furthermore, nine miRNAs were overexpressed and one underexpressed in integrated HPV-16 cell lines compared to the HPV-negative CaCx cell line C-33A. Based on microarray and/or quantitative realtime PCR and northern blot analyses, microRNA-218 (miR-218) was specifically underexpressed in HPV-positive cell lines, cervical lesions and cancer tissues containing HPV-16 DNA compared to both C-33A and the normal cervix. Expression of the E6 oncogene of high-risk HPV-16, but not that of low-risk HPV-6, reduced miR-218 expression, and conversely, RNA interference of E6/E7 oncogenes in an HPV-16-positive cell line increased miR-218 expression. We also demonstrate that the epithelial cell-specific marker LAMB3 is a target of miR-218. We also show that LAMB3 expression is increased in the presence of the HPV-16 E6 oncogene and this effect is mediated through miR-218. These findings may contribute to a better understanding of the molecular mechanisms involved in cervical carcinogenesis.
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