Dysregulated microRNAs involved in the progression of cervical neoplasm.

PURPOSE

MicroRNAs (miRNAs) exhibit dysregulated expression in human cancer and play an important role in carcinogenesis. The aim of this study was to identify a distinct miRNA expression signature for cervical cancer and cervical intraepithelial neoplasia (CIN) and to investigate the function of deregulated miRNAs in cervical carcinoma.

METHODS

A miRNA microarray was used to compare miRNA expression profiles in cervical cancer, CIN and normal cervical tissues. Real-time RT-PCR was used to validate the expression of 9 miRNAs in 103 cervical tissues. Bioinformatics programs were used to predict potential target genes and their function. Functional studies were performed to characterize the effect on cervical cancer cells by overexpression of miR-218 and miR-21.

RESULTS

We identified deregulated miRNAs in cervical cancer and high-grade squamous intraepithelial lesions (HSIL). MiR-218 was the most downregulated (0.175-fold decrease) miRNA, and miR-21 was the most upregulated (5.67-fold increase) miRNA. In addition, the expression patterns of 9 miRNAs were validated by real-time RT-PCR. Bioinformatics analyses and functional studies indicated that miR-218 and miR-21 may be involved in cancer invasion and metastasis.

CONCLUSION

Our study demonstrated that miRNAs are aberrantly expressed in cervical cancer and cervical preneoplastic lesions. These miRNAs may be involved in the progression of cervical neoplasm as potential tumor suppressor genes or oncogenes.