Prostate cancer is the second leading cause of cancer death in men in the United States. Recent evidence shows that some microRNAs (miRNAs) contribute to the malignant transformation and progression of prostate cancer. Both miR-15a and miR-16-1 are located at human chromosome 13q14 and transcribed as a cluster. Deletions or mutations of this region are frequently detected in clinical prostate cancer samples. It is well known that overexpression of growth factors and/or growth factor receptors contribute to the malignant phenotype in numerous cancer types. We hypothesize that growth factor signaling may be regulated by the miR-15a/miR-16-1 cluster in prostate cancer. In silico analysis revealed two putative miR-15a/miR-16-1 target sites in the 3\#8217; untranslated region (3\#8217;UTR) of basic fibroblast growth factor (FGF2); frequently up-regulated in prostate and other tumor types. Transfection of miR-16-1 into prostate (PC-3 and DU-145), renal (A498), colon (HCT116), and cervical (Hela) cancer cell lines significantly reduced FGF2 expression levels. Cloning of the target sites into a luciferase 3\#8217;UTR reporter vector further revealed that FGF2 is directly regulated by miR-15a and miR-16-1. Analysis of downstream signaling factors also indicated that activation of ERK was inhibited by miR-16-1. Our results suggest that the miR-15a/miR-16-1 cluster may contribute to the malignant phenotype of prostate and other cancers, in part, by directly regulating FGF2 levels.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2536.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009