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ABSTRACT

BACKGROUND This study presents a prediction of putative miRNA within several Human Papillomavirus (HPV) types by using bioinformatics tools and a strategy based on sequence and structure alignment. Currently, little is known about HPV miRNAs. METHODS Computational methods have been widely applied in the identification of novel miRNAs when analyzing genome sequences. Here, ten whole-genome sequences from HPV-6, -11, -16, -18, -31, -33, -35, -45, -52, and -58 were analyzed. Software based on local contiguous structure-sequence features and support vector machine (SVM), as well as additional bioinformatics tools, were utilized for identification and classification of real and pseudo microRNA precursors. RESULTS An initial analysis predicted 200 putative pre-miRNAs for all the ten HPV genome variants. To derive a smaller set of pre-miRNAs candidates, stringent validation criteria was conducted by applying <‒10 ΔG value (Gibbs Free Energy). Thus, only pre-miRNAs with total scores above the cut-off points of 90% were considered as putative pre-miRNAs. As a result of this strategy, 19 pre-miRNAs were selected (hpv-pre-miRNAs). These novel pre-miRNAs were located in different clusters within HPV genomes and some of them were positioned at splice regions. Additionally, the 19 identified pre-miRNAs sequences varied between HPV genotypes. Interestingly, the newly identified miRNAs, 297, 27b, 500, 501-5, and 509-3-5p, were closely implicated in carcinogenesis participating in cellular longevity, cell cycle, metastasis, apoptosis evasion, tissue invasion and cellular growth pathways. CONCLUSIONS The novel putative miRNAs candidates could be promising biomarkers of HPV infection and furthermore, could be targeted for potential therapeutic interventions in HPV-induced malignancies.

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