Abstract:

Objective To analyze the expression of microRNA-223 （miR-223） in the ovarian cancer tissue and explore the effect of miR-223 on the proliferation and invasion of ovarian cancer OVCAR3 cells， and to clarify the molecular regulatory mechanism. Methods The expression levels of miR-223 in tissue samples taken during surgical removal of 45 patients with ovarian cancer and different ovarian cancer cells were detected by real-time fluorescence quantitative PCR （RT-qPCR） method， and the expression levels of miR-223 in cancer tissue of the ovarian cancer patients with different clinicopathological features were analyzed. The ovarian cancer OVCAR3 cells were cultured in vitro； bioinformatics， dual luciferase reporter gene experiment and Western blotting method were used to analyze the targeted regulation relationship of miR-223 to N-myc downstream regulatory gene 1 （NDRG1）. The OVCAR3 cells were transfected with negative control mimic（NC group），miR-223 inhibitor（MiR in group） and miR-223 inhibitor and siRNA-NDRG1 plasmid at the same time（MiR in+si-NDRG1 group）. The number of clone formation was detected by colony formation test， the apoptotic rate was measured by flow cytometry， and the number of invasion cells was measured by Transwell chamber assay. Results Compared with adjacent normal tissue the expression level of miR-223 in cancer tissue was significantly increased（P<0.01）；the miR-223 expression level was closely related to the degree of histological differentiation， FIGO stage and lymph node metastasis of ovarian cancer patients （P<0.01）. Meanwhile， the expression levels of miR-223 in the different ovarian cancer cells were higher than that in normal ovarian epithelial cells（P<0.01）. MiR-223 could target NDRG1 and inhibit the expression of NDRG1， and the expression level of NDRG1 mRNA in ovarian cancer tissue was negatively correlated with the expression level of miR-223 （r=－0.291， P<0.01）. Compared with NC group， the number of clone formation and the number of invasion cells in MiR in group were decreased （P<0.05 or P<0.01）， while the apoptotic rate was significantly increased（P<0.01）. Compared with MiR in group， the number of clone formation and the number of invasion cells in MiR in + si-NDRG1 group were increased （P<0.05 or P<0.01）， while the apoptotic rate was decreased （P<0.01）. Conclusion MiR-223 is highly expressed in the ovarian cancer tissue， which is positively correlated with the severity of ovarian cancer. MiR-223 can promote the proliferation and invasion of ovarian cancer cells and inhibit apoptosis by targeted inhibition of NDRG1 expression.

Key words: MiR-223, N-myc downstream regulatory gene 1, Ovarine neoplasms, Cell proliferation, Cell invasion