MiR-143Inhibits The Metastasis Of Pancreatic Cancer And The Possible Mechanisms

Purpose:Pancreatic cancer is characterized by early metastasis and high mortality. In this study, the role of miR-143in invasion and metastasis and the possible mechanisms was investigated in pancreatic cancer cells in vitro and in vivo.Methods:miR-143expression was established by an adenovirus-carried miR-143expression cassette. mRNA and protein levels of gene expression were examined by RT-PCR and Western blot assay, respectively. Rho GTPases activity was measured by the pull down assay. The role of miR-143in migration and invasion of Panc-1cells was tested in vitro. The antimetastatic effect of miR-143was tested in a liver metastasis model, while its antitumor growth effect was tested in a xenograft Panc-1tumor model.Results:Results demonstrated that ARHGEF1(GEF1), ARHGEF2(GEF2), and K-RAS genes are the targets of miR-143. miR-143expression significantly decreased mRNA and protein levels of GEF1, GEF2, and K-RAS genes; lowered the constitutive activities of RhoA, Rac1, and Cdc42GTPases; decreased the protein levels of MMP-2and MMP-9; but significantly increased the protein level of E-cadherin. miR-143expression also significantly inhibited the migration and invasion of Panc-1cells in vitro, liver metastasis, and xenograft tumor growth in vivo.Conclusion:Our study suggested that miR-143plays an important role in the invasion and metastasis of pancreatic cancer, loss of miR-143’s (low) expression may be an important reason to cause pancreatic cancer highly invasive and metastatic and miR-143is a potential target for pancreatic cancer therapy.