Mechanism of miR-21 via Wnt/β -catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice

Objective: To study the mechanism of effect of miR-21 via Wnt/beta -catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice. Methods: The effect of miR-21 on A549 cells were detected by MTT method. MiR-21 expression levels were overexpressed or inhibited in A549 cells by transfecting with miR-21 mimics or inhibitors. Correlation among key molecules (Wntl, beta-catenin, CyclinD1 and miR-21) of mRNA and protein levels in Wnt/beta-catenin signaling pathway were studied by Real-time PCR and Western blot hybridization assay. Invasive ability of A549 cells was determined via Transwell chamber cell invasion assay; the role of miR-21 in A549 cells was explored via the Wnt/ beta-catenin signaling pathway. A Lewis lung carcinoma animal model was established to detect miR-21 expressions in tumor animals and controlled animal tissues, and verify expression changes of the above moleculesin the Wnt / beta-catenin signaling pathway was determined in the animal level. Results: MTT assay results showed that miR-21 overexpression could markedly enhance cell absorbance value; that is, miR-2 I could increase the ability proliferation of A549 cells. beta-catenin and CyclinD1 expression levels were significantly higher in miR-2l mimic transfected cells (P<0.05), and Writ! gene had no significant change. Wad, 13 cater-tin and CyclinD1 gene expression showed no significant change when miR-2I expression was suppressed. compared with controls. After cells were transfected with miR-2I mimics, cell invasion assay revealed that the perforated cells was significantly higher than the perforated cells in the control group (P<0.01). Lewis lung assay revealed that miR-21 expression levels in the Lewis lung carcinoma were significantly higher; and at the same time, Wnt1, beta-catenia and CyclinD1 gene expression levels were significantly increased, compared to controls. Conclusions: In A549 human lung cancer cells and Lewis lung carcinoma in mice, key molecules beta -catenin and CyclinDlof miR-2I expressions and the Wnt/ beta -catenin signaling pathway are positively correlated.