hsa-miR-520h downregulates ABCG2 in pancreatic cancer cells to inhibit migration, invasion, and side populations

BACKGROUND: Expression of ABCG2 is normally absent or low in the pancreas, but high in human pancreatic cancer cells. The mechanism by which ABCG2 is altered in human cancers remains unknown. METHODS: We investigated ABCG2 expression in four pancreatic cancer cell lines, and used three microRNA (miRNA) target prediction programmes, and information from the existing literature to predict and identify hsa-miR-520h as an miRNA that targets ABCG2. The function of this miRNA was investigated by transient transfection of the pancreatic cancer cell line PANC-1 with oligonucleotides that mimic hsa-miR-520h. RESULTS: Results showed that both mRNA and protein levels of ABCG2 were reduced, indicating that it was a target of hsa-miR-520h. Introduction of hsa-miR-520h mimics into PANC-1 cells also resulted in inhibition of cell migration and invasion, and reduction of side population cells. Cell proliferation, cell cycle progression and apoptosis were not affected. CONCLUSIONS: We propose that the effects of hsa-miR-520h may be, at least in part, caused by its regulation of ABCG2. Thus, our findings provide a new insight into the function of miRNA in the regulation of ABCG2 expression in pancreatic cancer. Gene therapy using miRNA mimics may therefore be useful as a pancreatic cancer therapy. British Journal of Cancer (2010) 103, 567-574. doi:10.1038/sj.bjc.6605724 www.bjcancer.com Published online 13 July 2010 (C) 2010 Cancer Research UK