Metformin alters the expression profiles of microRNAs in human pancreatic cancer cells.

AIMS

To investigate the effect of metformin on the expression profiles of microRNAs in human pancreatic cancer cells.

METHODS

MicroRNAs real-time PCR Array was applied to investigate differentially expressed miRNAs in Sw1990 cells treated with or without metformin. Stem-loop real time RT-PCR was used to confirm the results of the array assay in Sw1990 and Panc-1 cells. The effects of miR-26a on cell growth, apoptosis, invasion and migration abilities were respectively examined by CCK8 assay, Apoptosis assay, Matrigel invasion and migration assay. HMGA1 was proved to be a target of miR-26a by Luciferase reporter assay, Real-time PCR and Western-blotting.

RESULTS

Nine miRNAs were significantly up-regulated in metformin treated cells. Metformin up-regulated the expression of miR-26a, miR-192 and let-7c in a dose-dependent manner. Forced expression of miR-26a significantly inhibited cell proliferation, invasion, migration and increased cell apoptosis, whereas knockdown of miR-26a obtained the opposite effect. Furthermore, we demonstrated that HMGA1, an oncogene, is a direct target of miR-26a. Nude mice xenograft models confirmed that metformin up-regulated the level of miR-26a and surpressed the expression of HMGA1 in vivo.

CONCLUSION

These observations suggested that modulation of miRNA expression may be an important mechanism underlying the biological effects of metformin.