miR-21 promotes growth, invasion and migration of lung cancer cells by AKT/P-AKT/cleaved-caspase 3/MMP-2/MMP-9 signaling pathway.
Haiquan Li, Jie Zhao, Xiaomin Jia, Yanmin Zhang, Yongliang Du, Huiting Li, Lei Ma, Jian‐An Huang
Abstract
OBJECTIVE: This study aimed to demonstrate the effects of miR-21 on the growth, migration, and invasion of lung cancer cells A549 in vitro and the possible mechanism. METHODS: In vitro cell migration and invasion potential were determined by Transwell chamber assays. FACS was used to assess the effect of miR-21 on A549 cell cycle and apoptosis. 4-6 week-old female mice were utilized to establish a lung cancer model. The pathologic biopsy was processed by H&E staining. The expression of the proteins PTEN, RECK and Caspase 3 were detected through immunohistochemy and tumor cell apoptosis was measured by TUNEL. RESULTS: Transwell chamber assays showed that the cells going through the membrane increased significantly compared to the negative control (P<0.05). The tumor volume resulting from miR-21 mimics was significantly greater than in normal mice. Serum ELISA showed that the protein expression levels of MMP-2 and MMP-9 in miR-21 overexpression group were increased significantly. In addition, H&E staining results showed that in miR-21 overexpression tissue, invasion is more severe and immunohistochemical results proved that the miR-21 overexpression group had high expression of Caspase 3 protein but the expression of PTEN and RECK were decreased. TUNEL experiments show that increased the expression of miR-21 can inhibit the apoptosis of tumor cells. CONCLUSION: MicroRNA-21 promotes the proliferation of lung cancer cells and inhibits the apoptosis of lung cancer cells by the AKT/P-AKT/cleaved-caspase 3/MMP-2/MMP-9 signaling pathway.