MBP-1 upregulates miR-29b, which represses Mcl-1, collagens, and matrix metalloproteinase-2 in prostate cancer cells

Abstract

c-myc promoter binding protein (MBP-1) is a multifunctional protein known to regulate expression of targets involved in the malignant phenotype. We have previously demonstrated that exogenous expression of MBP-1 inhibits prostate tumor growth, although the mechanism of growth inhibition is not well understood. We hypothesized that MBP-1 may modulate microRNA (miRNA) expression for regulation of prostate cancer cell growth. In this study, we demonstrated that exogenous MBP-1 upregulates miR-29b by 5- to 9-fold in prostate cancer cells as measured by real-time quantitative reverse transcription polymerase chain reaction. Subsequent studies indicated that exogenous expression of miR-29b inhibited Mcl-1, COL1A1, and COL4A1. Furthermore, a novel target with potential implications for invasion and metastasis, matrix metallopeptidase-2 (MMP-2), was identified and confirmed to be a miR-29b target in prostate cancer cells. Together, these results demonstrated that exogenous expression of miR-29b regulates prostate cancer cell growth by modulating antiapoptotic and prometastatic matrix molecules, implicating the therapeutic potential of miR-29b for prostate cancer inhibition.