Research papermiR-34a and its novel target, NLRC5, are associated with HPV16 persistence

- miR-34a and NLRC5 are associated with HPV16 persistence.
- NLRC5 interacts with miR-34a.
- Upregulation of NLRC5 is concurrent with downregulation of miR-34a in human cervical samples with HPV16 persistence.
- Our data uncover a previously unknown connection between the HPV16 persistence and miR-34a which directly targets to NLRC5.
- The reverse expression pattern of NLRC5 and miR-34a might be involved in the interference of HPV16 with host defense system.

Persistent infection with human papillomavirus (HPV), particularly type 16, is causally associated with cervical cancer and its precursors. The role of miRNAs in HPV16 persistence currently remains unclear. Preliminary analysis of miRNA profile demonstrated that HPV16 infection caused a striking downregulation of miR-34a. Through bioinformatics analysis and dual-luciferase assay with site-directed mutagenesis strategy, NLRC5, a negative regulator of NF-κB signaling, was identified to be a novel interactor of miR-34a. Transfection of miR-34a mimic strikingly downregulated NLRC5 in the HPV16-positive cervical cells, which might result in the nuclear accumulation of NF-κB p65. However, transfection of miR-34a inhibitor exhibited an opposite effect. The antagonistic expressions of NLRC5 and miR-34a were also observed in keratinocytes harboring HPV16 genome as well as in human cervical samples with persistent infection of HPV16. Our data uncover a previously unknown connection among HPV16 persistence, miR-34a and its interactor NLRC5.