Abstract 1948: Pvt1-encoded microRNA miR-1204 in tumorigenesis of human ovarian and breast cancer

Amplification at chromosome 8q24 is one of the most frequent genomic abnormalities in human cancers and is associated with reduced survival duration in ovarian and breast cancers. Recently, microRNAs (miRNAs) at 8q24 have been identified in the PVT1 locus. Herein, we explored the biological functions of one miRNA, miR-1204, residing within the exon1B of PVT1. Mature hsa-mir-1204 is over-expressed in PVT1 amplified ovarian and breast cancer cell lines (HEY, OVCAR8, SUM-159PT and MDA-MB231). In vitro treatment with antagomir against hsa-mir-1204 inhibited cell proliferation and induced apoptosis in the four PVT1 amplified ovarian and breast cancer lines. Conversely, over-expression of miR-1204 promoted cell growth in PVT1 non-amplified ovarian and breast cancer lines (OV90 and MCF10A) and cooperated with c-Myc to potentiate Rat1A cell colony growth in soft agar assays. Since an inverse expression pattern is often present between miRNA and its target genes, we used computational approaches (miRanda, TargetScan, Pita) to identify distinct miR-1204 candidate target genes from two independent expression microarray datasets, one with significantly down-regulated genes by PVT1 copy number gain in 147 breast tumors and the other involving genes significantly repressed by miR-1204 overexpression and derepressed by silencing of miR-1204 in ovarian and breast cancer cells. Thirty putative target genes of miR-1204 were empirically verified by Q-RT-PCR method, and this group of genes was enriched with genes regulating cell death, cell growth and proliferation, cell cycle, cellular assembly and organization. Combined, these data suggest that human miR-1204 contributes to ovarian and breast tumor proliferation and survival and down-regulates distinct targets including multiple tumor suppressor genes and serves as a potential therapeutic target against tumors with 8q24 amplification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1948.