MicroRNA Analysis in Human Papillomavirus (HPV)-Associated Cervical Neoplasia and Cancer

Abstract

Background: MicroRNAs (miRNAs) are ~22 nt single-stranded, non-coding RNAs that generally negatively regulate their target mRNAs at a posttranscriptional level. Differential expression of miRNAs has been observed in many human cancers. Methods: To study their potential role in the pathogenesis of human papillomavirus (HPV) type 16-associated cervical neoplasia and cancer, we analyzed miRNA expression in cervical tissue from the normal cervix, moderate/ severe dysplasia, and invasive squamous cell carcinoma. Results: Using RNA from six cervical cancers, three dysplasias, and four normal samples and the TaqMan® MicroRNA Arrays, we found that 18 miRNAs were overexpressed and 2 underexpressed in cervical cancer compared to normal cervical tissue. We further demonstrated via individual TaqMan® MicroRNA Assays that 8 miRNAs (miRs- 16, 21, 106b, 135b, 141, 223, 301b, and 449a) were significantly overexpressed and 2 miRNAs (miRs-218 and 433) were significantly underexpressed in cervical cancer compared to normal cervical tissue. MiR-21, miR-135b, miR- 223, and miR-301b were overexpressed in cervical cancer compared to both cervical dysplasia and normal tissue. MiR-218 was similarly underexpressed in cervical cancer compared to dysplasia and normal tissue. Conclusions: Our results suggest that ten miRNAs can delineate cervical cancer from normal cervical tissue, and five miRNAs may have potential as markers for progression from dysplasia to invasive cervical disease.