miRNAs are small non-coding mRNA binding nucleic acids which exhibit regulatory properties. It is known that their expression is significantly different between HPV-positive und –negative head and neck carcinomas. Previously, 36 miRNAs were described as being differentially expressed in these tumours [1]. So far, it was not analysed if this differential miRNA expression is relevant in the context of the known inverse correlation between HPV-status and expression of the antileukoprotease SLPI.
In 126 tonsillar carcinomas with known HPV-status (42.06% positive) and SLPI-protein expression levels, the 4 highest modulated miRNAs (miRNA 363, miRNA 21, miRNAs 31 und 193b*) [1] were analysed by RT-q-PCR and their correlation between HPV-status and SLPI-expression was determined. In silico, the SLPI sequence was screened for potential binding sites of the 36 differentially expressed miRNAs. Kaplan-Meier-Analysis was performed correlating HPV-status, SLPI- and miRNA-expression levels with overall- and progression free-survival.
Results indicate a 12- and 6-fold up-regulation of miRNA 363 and miRNA 21, respectively, and a 5-fold down-regulation of miRNAs 31 und 193b* in HPV-positive versus HPV-negative tonsillar carcinomas. Interestingly, the most up-regulated miRNA, namely miRNA 363, is the only one without potential binding sites in the SLPI-mRNA, however, potential binding to HPV mRNAs E6 and E7 is possible. In addition miRNA 363 shows the highest expression levels in HPV-positive but SPLI-negative carcinomas. HPV-positivity, as well as low SLPI- and high miRNA 363-expression levels are correlated with significantly better overall and progression free survival (all p<0.05).
Firstly, the results confirm the findings by Lajer and coworkers [1] with divergent expression levels in HPV-positive carcinomas and with miRNA 363 as the most up-regulated miRNA. The here, for the first time described, interplay between SLPI-expression and HPV-status on the one hand and the relation of miRNA 363 with HPV-positive but SPLI-negative carcinomas on the other hand, as well as the prognostic value of miRNA 363 suggests a role for this miRNA in the SLPI-modulated HPV-infection of tonsillar, but possibly also in all head and neck carcinomas.
[1] C.B. Lajer et al. (2012) Br J Cancer 106(9):1526-1534.