It involves microRNAs (miRNAs), an evolutionarily conserved class of small RNAs that suppress gene expression post-transcriptionally. Alterations in miRNA expression have been identified in various cancers resulting in their functioning as oncogenes, tumor suppressor genes or influencing metastasis. These researchers sought to identify microRNA that regulates metastatic prostate cancer. They performed microRNA expression profiling in human prostate cell lines to identify dysregulated microRNA components of advanced prostate cancer. miR-203 expression was identified and assessed in prostate carcinoma cell lines and clinical specimens by quantitative real-time PCR and in situ hybridization. miR-203 was re-expressed in bone metastatic prostate cancer cell lines followed by in vitro and in vivo functional assays.
They found miR-203 expression was specifically attenuated in bone metastatic prostate cancer suggesting a fundamental anti-metastatic role for this miRNA. Re-expression of miR-203 in bone metastatic prostate cancer cell lines suppressed metastasis via inhibition of several critical steps of the metastatic cascade including epithelial-mesenchymal transition, invasion and motility. Ectopic miR-203 significantly attenuated the development of metastasis in a bone metastatic model of prostate cancer. Importantly, miR-203 regulated a cohort of pro-metastatic genes including ZEB2, Bmi (polycomb repressor), Survivin and bone specific effectors including Runx2, a master regulator of bone metastasis. These findings suggest that miR-203 acts at multiple steps of the prostate cancer metastatic cascade via repression of a cohort of pro-metastatic targets.
Presented by Sharanjot Saini, et al. at the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.