MicroRNA-196a promotes cervical cancer proliferation through the regulation of FOXO1 and p27Kip1.

BACKGROUND

The phosphoinositide 3-kinase (PI3K)/Akt signalling pathway appears to be a key regulator in cervical carcinogenesis. However, the downstream regulatory mechanism of PI3K/Akt signalling remains largely unknown.

METHODS

The expression of miR-196a in cervical cancer cell lines and cervical cancer tissues was examined using real-time PCR. The effects of miR-196a on PI3K/Akt signalling and cellular proliferation were evaluated by bromodeoxyuridine labelling, 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide, colony formation assays and luciferase assays.

RESULTS

The expression level of miR-196a was markedly increased in cervical cancer tissues and cell lines compared with normal cervical tissue and normal cervical squamous cells. Upregulation of miR-196a was correlated with advanced tumour stage and poor overall and recurrence-free survival in cervical cancer patients. Upregulation of miR-196a enhanced G1/S-phase transition and the proliferative ability of cervical cancer cells, whereas suppression of miR-196a had the opposite effect. Using bioinformatics and biological approaches, we showed that FOXO1 and p27(Kip1), two key effectors of PI3K/Akt signalling, were direct targets of miR-196a.

CONCLUSIONS

Our findings suggest that miR-196a has an important role in promoting human cervical cancer cell proliferation and may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in cervical cancer.