Human Gene Set: BONCI_TARGETS_OF_MIR15A_AND_MIR16_1


Standard name BONCI_TARGETS_OF_MIR15A_AND_MIR16_1
Systematic name M11682
Brief description Potential targets of MIR15A and MIR16-1 [GeneID=406948;406950] microRNAs in prostate cancer.
Full description or abstract MicroRNAs (miRNAs) are noncoding small RNAs that repress protein translation by targeting specific messenger RNAs. miR-15a and miR-16-1 act as putative tumor suppressors by targeting the oncogene BCL2. These miRNAs form a cluster at the chromosomal region 13q14, which is frequently deleted in cancer. Here, we report that the miR-15a and miR-16-1 cluster targets CCND1 (encoding cyclin D1) and WNT3A, which promotes several tumorigenic features such as survival, proliferation and invasion. In cancer cells of advanced prostate tumors, the miR-15a and miR-16 level is significantly decreased, whereas the expression of BCL2, CCND1 and WNT3A is inversely upregulated. Delivery of antagomirs specific for miR-15a and miR-16 to normal mouse prostate results in marked hyperplasia, and knockdown of miR-15a and miR-16 promotes survival, proliferation and invasiveness of untransformed prostate cells, which become tumorigenic in immunodeficient NOD-SCID mice. Conversely, reconstitution of miR-15a and miR-16-1 expression results in growth arrest, apoptosis and marked regression of prostate tumor xenografts. Altogether, we propose that miR-15a and miR-16 act as tumor suppressor genes in prostate cancer through the control of cell survival, proliferation and invasion. These findings have therapeutic implications and may be exploited for future treatment of prostate cancer.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18931683   Authors: Bonci D,Coppola V,Musumeci M,Addario A,Giuffrida R,Memeo L,D'Urso L,Pagliuca A,Biffoni M,Labbaye C,Bartucci M,Muto G,Peschle C,De Maria R
Exact source Table 2S
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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Version history 3.0: First introduced

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