Abstract

BACKGROUND:Expression of ABCG2 is normally absent or low inthe pancreas, but high in human pancreatic cancer cells. The mechanism by whichABCG2 is altered in human cancers remains unknown.

METHODS:We investigated ABCG2 expression in four pancreaticcancer cell lines, and used three microRNA (miRNA) target predictionprogrammes, and information from the existing literature to predict andidentify hsa-miR-520h as an miRNA that targets ABCG2. The function of thismiRNA was investigated by transient transfection of the pancreatic cancer cellline PANC-1 with oligonucleotides that mimic hsa-miR-520h.

RESULTS:Results showed that both mRNA and protein levels ofABCG2 were reduced, indicating that it was a target of hsa-miR-520h.Introduction of hsa-miR-520h mimics into PANC-1 cells also resulted ininhibition of cell migration and invasion, and reduction of side populationcells. Cell proliferation, cell cycle progression and apoptosis were notaffected.

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 providea new insight into the function of miRNA in the regulation of ABCG2 expressionin pancreatic cancer. Gene therapy using miRNA mimics may therefore be usefulas a pancreatic cancer therapy.