miR-1180 Targets FXYD5 to Regulate Pancreatic Cancer Cells Migration and Invasion.

Abstract

Pancreatic cancer is a fatal malignancy typically diagnosed in older males and has an aggressive progression. The function of the miR-1180/FXYD5 axis in pancreatic cancer malignant behaviors was investigated. 20 pairs of pancreatic cancer and adjacent normal tissue samples were harvested from pancreatic cancer patients, and qRT-PCR, IHC, and western blot assays were performed, respectively, to detect the mRNA expression and protein levels of miR-1180 or FXYD5. Transwell and scratch assays were conducted to detect the migratory and invasive ability of pancreatic cancer cells; a Dual-luciferase reporter assay was employed to validate miR-1180 targeting FXYD5. miR-1180 targeting FXYD5 to regulate the migratory and invasive ability of pancreatic cancer cells was validated in mouse xenograft tumor models. FXYD5 expression was increased in pancreatic cancer tissue samples than in adjacent normal tissue samples (P < 0.01), and FXYD5 expression exhibited a positive correlation with the migratory and invasive ability of pancreatic cancer cells. miR-1180 targeted FXYD5 and negatively regulated FXYD5. Restoring miR-1180 expression could inhibit the migratory and invasive ability of pancreatic cancer cells (P < 0.01), and this effect could potentially be alleviated by FXYD5 overexpression. The miR-1180/FXYD5 axis positively regulated E-cadherin and negatively regulated MMP2 and MMP9 expression levels. In vivo findings demonstrated that miR-1180 overexpression inhibited tumor growth and lung metastasis (P < 0.05), while FXYD5 overexpression promoted tumor growth and lung metastasis (P < 0.05). In conclusion, the miR-1180 /FXYD5 axis could be involved in pancreatic cancer metastasis through the regulation of EMT and extracellular matrix degradation.