Lung cancer is the leading cause of cancer death in most economically developed countries. Recently amplification and overexpression of the miR-17-92 microRNA (miRNA) was found in lung cancer. This miRNA has been suggested to play a role in B-cell lymphoma development. Therefore the miR-17-92 overexpression in human cancers may have important roles in cancer development, but only a few targets for the miR-17-92 cluster have been identified thus. In this research study, we investigated target proteins for miR-17-92 using iTRAQ® reagents followed nano-LC-ESI-QqTOF mass spectrometer. 479 proteins were identified and quantified using ProteinPilotTM 2.0 software. The number of proteins which was more than a 2-fold down-regulation in the miR-17-92 transfected clone was eight. Four of the eight proteins with significant down-regulation, PGK1, ENO2, ENO1, TP11, are in the glycolytic pathway and six of the eight proteins lacked potential target sites for the miRNAs comprising the miR-17-92 cluster. Down-regulation of multiple proteins lacking potential target sites for miR-17-92 suggested the possibility that miR-17-92 could target a key transcription factor that commonly regulates their expression. We consequently discovered that HIF-1α, a well-known molecule regulating the glycolytic pathway, was computationally predicted to be a target for multiple miRNAs comprising the miR-17-92 cluster. Significant down-regulation of HIF-1α protein in BEAS2B cells was confirmed by Western blot analysis.
