MiR-4282 is a tumor-suppressor gene for preventing metastasis of epithelial ovarian cancer by negatively regulating MIER1.

OBJECTIVE

To elucidate the biological role of miR-4282 in influencing metastasis of epithelial ovarian cancer (EOC) by regulating MIER1.

PATIENTS AND METHODS

MiR-4282 expressions in 45 cases of EOC specimens and normal controls were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between miR-4282 and clinical features in EOC patients, including pathological indicators and overall survival, was analyzed. After intervening miR-4282 level in SKOV3 and 3AO cells by plasmid transfection, changes in migratory and invasive abilities were determined by transwell assay and wound healing assay. The target gene of miR-4282 was observed by Dual-Luciferase reporter assay, followed by exploration of its involvement in EOC progression via rescue experiments.

RESULTS

MiR-4282 was downregulated in EOC specimens than normal controls. EOC patients expressing low level of miR-4282 had higher incidences of lymphatic metastasis and distant metastasis, as well as worse prognosis than those overexpressing miR-4282. Overexpression of miR-4282 in SKOV3 cells weakened metastatic ability, and conversely, knockdown of miR-4282 in 3AO cells yielded the promotive trends. MIER1 was confirmed to be the target gene binding miR-4282, which was highly expressed in EOC specimens. MIER1 was able to reverse the regulatory effect of miR-4282 on EOC cell metastasis.

CONCLUSIONS

Lowly expressed miR-4282 in EOC specimens is closely linked to the incidence of metastasis and overall survival. MiR-4282 prevents EOC metastasis by a negative regulation on MIER1.