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hsa-miR-141 downregulates TM4SF1 to inhibit pancreatic cancer cell invasion and migration
发布时间:2016-11-28   浏览次数:977

Abstract

Expression of thetransmembrane-4-L-six-family-1 (TM4SF1) is high in human pancreatic cancercells, but the underlying mechanism remains unclear. In this study, we aimed toidentify and characterize microRNAs that regulate TM4SF1 expression in PCcells. Western blot analysis and quantitative polymerase chain reaction wereused to detect TM4SF1 and hsa-miR-141 levels in four PC cell lines. SW1990 andBxPc-3 cells were transfected with the inhibitor miR-141, the inhibitornegative control, the miR-141 mimic and the mimic negative control; and cellinvasion, migration, proliferation, cell cycle progression and apoptosis weredetected by Transwell, MTT and flow cytometry assays, respectively. The miR-141levels negatively correlated with the TM4SF1 protein levels in PC cells. TheTM4SF1 protein levels were lower in the 141M group but higher in the 141Igroup, although the TM4SF1 mRNA levels had no significant changes, compared tothe negative controls. Luciferase assays demonstrated that hsa-miR-141 directlytargeted the 3'-untranslated region of the TM4SF1 gene. In addition, miR-141downregulated TM4SF1 expression to inhibit invasion and migration of PC cellsbut had no effects on cell proliferation, cell cycle progression or apoptosis.TM4SF1 is a direct target of miR-141. Our findings that TM4SF1 expression wasinhibited by miR-141 provide new insights into the oncogenic mechanism ofTM4SF1 and suggest that miR-141 represents a novel molecular target for PCtherapy.