The expression of microRNA-145 in cervical cancer and its inhibitory effects on Wnt/β-catenin signaling pathway / 中国肿瘤临床

ABSTRACT

Objective: To explore the clinic-pathological significance of microRNA-145 expression in human cervical cancer and its ef-fects on Wnt/β-catenin signaling pathway. Methods: Real-time PCR was used to detect the expression of microRNA-145 in 62 cervical cancer samples. The correlation between microRNA-145 expression and the clinic-pathological parameters and its prognostic signifi-cance was analyzed. MicroRNA-145-expressing plasmid and non-sense plasmid were transfected into human cervical cancer HeLa cells, assigned into overexpressed microRNA-145 group and control group. Immunofluorescence staining was performed to detect the expression location of β-catenin. Top Flash luciferase reporter assay was performed to investigate the effects of microRNA-145 on the transcriptional activity of TCF/LEF and direct interactions with Catenin&delta;-1. Western blot was used to detect the effects of microRNA-145 on the expression of Catenin&delta;-1, C-MYC, and CyclinD1. Results: The patients with low microRNA-145 expression showed poorer prognosis [(41.28 ± 2.00) months vs . (46.06 ± 0.95) months, P<0.05]. β-catenin immunofluorescence was distributed within the cyto-plasm in the microRNA-145-overexpressed HeLa cells, but mainly within the nucleus and cytoplasm in the control cells. The luciferase reporter system indicated that the transcriptional activity of TCF/LEF was inhibited in the microRNA-145-overexpressed HeLa cells, and validated Catenin&delta;-1 was a target of miR-145. The expression of Catenin&delta;-1, C-MYC, and CyclinD1 was decreased in the microRNA-145-overexpressed HeLa cells. Conclusions: microRNA-145 may inhibit cervical cancer progression via Catenin&delta;-1 and inhibit the Wnt/β-catenin signaling pathway.