MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor

Background: Increasing evidence has shown that microRNAs function as oncogenes or tumor suppressors in human malignancies, but the roles of microRNA (miR)-497 in human cervical cancer still remain unclear. Our aim was to analyze the clinicopathologic and prognostic significance of miR-497 in human cervical cancer and to investigate the effects of miR-497 on the malignant phenotype of cervical cancer cells.

Methods: First, we detected miR-497 expression in the HPV-16-immortalized cervical epithelial cell lines and 4 other cervical cancer cell lines (HeLa, Caski, SiHa, and HeLa-S3). Then the expression of miR-497 was analyzed in cervical cancer tissues and paired nontumor tissues, and its correlation with clinicopathologic features and survival was analyzed. Finally, the roles of miR-497 in regulation of tumor proliferation, apoptosis, migration, invasion, and target gene expression were further investigated.

Results: MiR-497 was downregulated in cervical cancer cells or tissues compared with HPV-16-immortalized cervical epithelial cell lines or the paired nontumor tissues. Also, the decrease in miR-497 correlated closely with the criteria of the International Federation of Gynaecology and Obstetrics stage and lymph node metastases in patients with cervical cancer. Multivariate Cox analysis showed that low miR-497 expression appeared to be an unfavorable prognostic factor. Transient forced expression of miR-497 decreased the growth and colony-formation capacity of HeLa and SiHa cells by inducing Caspase-3-dependent apoptosis. Forced expression of miR-497 suppressed the migration and invasiveness of cervical cancer cells. By computational miRNA target prediction and functional analysis, miR-497 was demonstrated to bind to the 3' untranslated regions of IGF-1R mRNA, and upregulation of miR-497 downregulated IGF-1R protein expression. Further investigation showed that small interfering RNA-mediated IGF-1R knockdown could mimic the effect of enforced miR-497 expression on the malignant phenotypes of cervical cancer cells.

Conclusion: MiR-497 may be a potential prognostic marker and functions as a tumor suppressor in human cervical cancer by post-transcriptionally targeting IGF-1R.