Perturbation of DROSHA and DICER expression by human papillomavirus 16 oncoproteins

- DROSHA is frequently overexpressed due to gene amplification in human papillomavirus associated cancers.
- We showed that HPV16 E6 and E7 cause increased DROSHA and DICER expression.
- This is correlated to modulation of DROSHA regulated microRNAs in HPV16 E6/E7 expressing cells.

Many tumors, including cervical carcinoma, show dysregulated expression of the microRNA processing machinery, specifically DROSHA and DICER. Some cervical cancers exhibit chromosome 5p amplifications and DROSHA is the most significantly upregulated transcript and is observed in all tumors with 5p gain. DROSHA and DICER mRNA levels, however, are higher in HPV positive cancer lines than in an HPV negative cervical carcinoma line. We show that high-risk HPV E6/E7 expression in HPV negative C33A cervical carcinoma cells and primary human epithelial cell causes increased expression of DROSHA and DICER mRNA and protein. Most importantly, many DROSHA regulated microRNAs are dysregulated in HPV16 E6/E7 expressing cells. These results suggest that increased DROSHA levels contribute to HPV16 E6/E7 dysregulation of cellular microRNA expression.