Background/Aims: To reveal the microRNA (miRNA) expression signatures in cervical tissues and roles of miRNAs related with the progress of HPV carcinogenesis.
Methods: MiRNA characterization was analyzed by microarray in cervical biopsy tissues with or without HPV type 16 infections. The differentially expressed miRNAs, as verified by RT-PCR, were subjected to gene ontology (GO) analysis. Furthermore, the effects of mir-29 family, significantly enriched in biological pathways and predicted to target primary genes referred to HPV infection, on cell cycle were investigated. The underlying mechanism related to CDK6 and p16INK4a was assessed.
Results: 31 miRNA expressed differentially in invasive squamous cell carcinoma (SCC), cervical intraepithelial neoplasia (CIN)2-3 and normal tissues. And 13 downregulated and 13 upregulated miRNAs were found in cervical SCCs infected with HPV type 16, compared with normal tissues. The expression of mir-29, -375, -99a, -195 (underexpressed), -106a and -155 (overexpressed) was validated. High-enrichment miRNA-HPV-related gene networks characterized by mir-29 family, which targeted CDK6 and regulated the expression of p16INK4 indirectly, uncovered the critical role of mir-29 in HPV carcinogenesis. Restored expression of mir-29 suppressed the G1/S transition in cervical cancer cells.
Conclusions: The miRNA expression profiles may provide potential novel biomarkers and therapeutic strategies for cervical cancer, besides HPV. Mir-29 is a putative key tumor suppressor miRNA during HPV carcinogenesis.