Monday 28 November 2011
Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer.
microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, -99a, 26a, and 125b were the most abundantly expressed.
In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection.
A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis.
Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre-miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA.
HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes.
NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002).
Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002).
Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b.
Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells.
HPV L2-induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis.
Strong inverse correlation between microRNA-125b and human papillomavirus DNA in productive infection. Nuovo GJ, Wu X, Volinia S, Yan F, di Leva G, Chin N, Nicol AF, Jiang J, Otterson G, Schmittgen TD, Croce C. Diagn Mol Pathol. 2010 Sep;19(3):135-43. PMID: #20736742#