Background MicroRNA-25-3p (miR-25-3p) is a miRNA that is closely related to tumors. Zinc finger E-box binding homeobox 2 (ZEB2) is the target gene of miR-25-3p. However, whether miR-25-3p can play a role in the progression of cervical cancer by targeting ZEB2 is unclear.
Objective To investigate the clinical significance of miR-25-3p and ZEB2 expression in cervical cancer tissues and its effect on the proliferation and invasion of cervical cancer cells.
Methods A total of 84 patients with cervical cancer treated in West China (Sanya) Hospital of Sichuan University from January 2013 to December 2014 were selected. Another 40 cases of normal cervical tissues excised due to benign diseases were collected as the control. The mRNA and protein expression levels of ZEB2 and miR-25-3p in cervical cancer tissues and normal cervical tissues were detected. The relationship between the mRNA and protein expression levels of ZEB2 and miR-25-3p and the clinicopathological parameters and prognosis of cervical cancer patients was analyzed. Pearson linear correlation analysis was used to detect the correlation between miR-25-3p, mRNA and protein expression in cervical cancer tissues; HeLa cells were routinely cultured, divided into NC group, miR-25-3p mimic group and miR-25-3p + oe-ZEB2 group. MTS experiment was used to detect the proliferation ability of each group, and Boyden experiment was used to detect the invasion ability of each group.
Results The expression level of miR-25-3p in cervical cancer tissues was significantly lower than that in the normal cervical tissues (P＜0.05), and the expression levels of ZEB2 mRNA and protein in cervical cancer tissues were significantly higher than those in normal cervical tissues (P＜0.05). The expression level of miR-25-3p in cervical cancer tissues was correlated with lymph node metastasis, depth of myometrial invasion and FIGO stage (P＜0.05). The expression levels of ZEB2 mRNA and protein in cervical cancer tissues were correlated with histological grade, lymph node metastasis and FIGO stage (P＜0.05). Kaplan-Meier survival curve showed that the 5-year OS rate of cervical cancer patients in the miR-25-3p low expression group was lower than that in the miR-25-3p high expression group (P＜0.05), and the 5-year OS rate of cervical cancer patients with high ZEB2 mRNA and protein expression level was lower than that of ZEB2 low expression group (P＜0.05). The expression levels of miR-25-3p and ZEB2 in cervical cancer tissues were negatively correlated (P＜0.05). Target Scan7.1 software prediction and dual luciferase reporter gene experiment results showed that ZEB2 was the target gene of miR-25-3p. Compared with the NC group, the cell proliferation and invasion ability of the miR-25-3p mimic group and miR-25-3p+oe-ZEB2 group were reduced (P＜0.05). Compared with the miR-25-3p mimic group, the cell proliferation and invasionability of miR-25-3p+oe- ZEB2 group were increased (P＜0.05).
Conclusion miR-25-3p and ZEB2 are related to the adverse patho-logical parameters and prognosis of cervical cancer patients, and miR-25-3p negatively regulates ZEB2 to inhibit the proliferation and invasion of cervical cancer. miR-25-3p and ZEB2 may be new prognostic markers and therapeutic targets for cervical cancer.
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