Mek inhibitor suppresses expression of the mir-17-92 cluster with g1-phase arrest in ht-29 human colon cancer cells and mia paca-2 pancreatic cancer cells

Abstract

Background: MicroRNAs (miRNAs) are small non-coding RNAs, and the deregulated expression of miRNAs is associated with tumor development. Among these, the miR-17-92 cluster, including six mature miRNAs, is known as an oncogenic miRNA cluster because expression of the miR-17-92 cluster is frequently elevated in a variety of malignant tumors. Materials and Methods: We investigated whether a mitogen-activated protein kinase kinase (MEK) inhibitor, PD0325901, suppresses expression of the miR-17-92 cluster in HT-29 human colon cancer cells and MIA PaCa-2 pancreatic cancer cells. Results: PD0325901 inhibited cell growth with G1-phase arrest and suppressed expression of the miR-17-92 cluster. Furthermore, phosphatase and tensin homolog (PTEN), which is a target molecule of the miR-17-92 cluster, was up-regulated by PD0325901. The exogenous expression of miR-17 slightly, but significantly reduced G1-phase arrest by PD0325901. Conclusion: These results raise the possibility that a MEK inhibitor causes G1-phase arrest, at least partially, through suppression of the miR-17-92 cluster.