Study on the miR-431-5p inhibiting the proliferation, migration, invasion and promoting the apoptosis of pancreatic cancer cells by regulating AKT1

ObjectiveTo investigate the effects of miR-431-5p on the proliferation, migration, invasion and apoptosis of pancreatic cancer cells, and its underlying mechanism.

MethodsThe qRT-PCR was used to detect the expression levels of miR-431-5p in human normal pancreatic epithelial cells hTERT-HPNE and pancreatic cancer cells CFPAC-1 and PANC-1. After the miR-431-5p mimics were transfected into the pancreatic cancer CFPAC-1 cells to overexpress miR-431-5p, the MTT assay was used to detect the cell proliferation activity, the Transwell assay was used to detect the cell migration and invasion, the flow cytometry was used to detect the apoptosis, and the Western blotting was used to detect the expression levels of Cyclin D1, p21, Bax, Bcl-2, E-cadherin, MMP-2 and AKT1 proteins. The regulatory relationship between miR-431-5p and AKT1 was investigated using the dual luciferase reporter gene experiment.

ResultsCompared with hTERT-HPNE cells, the expression levels of miR-431-5p in pancreatic cancer cell PANC-1 and CFPAC-1 significantly decreased(P < 0.05). After the miR-431-5p in CFPAC-1 cells was overexpressed, the cells activity and number of migrating and invading cells decreased(P < 0.05), the apoptosis rate increased(P < 0.05), the expression levels of Cyclin D1, Bcl-2 and MMP-2 protein decreased(P < 0.05), and the expression levels of p21, Bax and E-cadherin protein increased(P < 0.05 to P < 0.01). The results of the dual luciferase reporter gene experiment showed that the miR-431-5p negatively regulated the AKT1 expression in CFPAC-1 cells. After the miR-431-5p and AKT1 in CFPAC-1 cells were overexpressed, the CFPAC-1 cell activity, the number of migrating and invading cells increased, the apoptosis rate decreased, the protein expression levels of Cyclin D1, Bcl-2 and MMP-2 increased, while the protein expression levels of p21, Bax and E-cadherin decreased, and the differences of which were statistically significant(P < 0.05).

ConclusionsThe miR-431-5p can inhibit the proliferation, migration and invasion of pancreatic cancer CFPAC-1 cells, and promote apoptosis by targeting AKT1. It may be a potential molecular therapeutic target for pancreatic cancer.