miR-99 Family of MicroRNAs Suppresses the Expression of Prostate-Specific Antigen and Prostate Cancer Cell Proliferation
- 14 February 2011
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 71 (4), 1313-1324
- https://doi.org/10.1158/0008-5472.can-10-1031
Abstract
MicroRNAs (miRNA) have been globally profiled in cancers but there tends to be poor agreement between studies including in the same cancers. In addition, few putative miRNA targets have been validated. To overcome the lack of reproducibility, we profiled miRNAs by next generation sequencing and locked nucleic acid miRNA microarrays and verified concordant changes by quantitative RT-PCR. Notably, miR-125b and the miR-99 family members miR-99a, -99b, and -100 were downregulated in all assays in advanced prostate cancer cell lines relative to the parental cell lines from which they were derived. All four miRNAs were also downregulated in human prostate tumor tissue compared with normal prostate. Transfection of miR-99a, -99b, or -100 inhibited the growth of prostate cancer cells and decreased the expression of prostate-specific antigen (PSA), suggesting potential roles as tumor suppressors in this setting. To identify targets of these miRNAs, we combined computational prediction of potential targets with experimental validation by microarray and polyribosomal loading analysis. Three direct targets of the miR-99 family that were validated in this manner were the chromatin-remodeling factors SMARCA5 and SMARCD1 and the growth regulatory kinase mTOR. We determined that PSA is posttranscriptionally regulated by the miR-99 family members, at least partially, by repression of SMARCA5. Together, our findings suggest key functions and targets of miR-99 family members in prostate cancer suppression and prognosis. Cancer Res; 71(4); 1313–24. ©2011 AACR.Keywords
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This publication has 47 references indexed in Scilit:
- FKBP51 and Cyp40 are positive regulators of androgen-dependent prostate cancer cell growth and the targets of FK506 and cyclosporin AOncogene, 2009
- Towards the definition of prostate cancer-related microRNAs: where are we now?Trends in Molecular Medicine, 2009
- Regulation of androgen receptor transcriptional activity by rapamycin in prostate cancer cell proliferation and survivalOncogene, 2008
- The impact of microRNAs on protein outputNature, 2008
- The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target geneProceedings of the National Academy of Sciences, 2008
- Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cellsJournal of Molecular Medicine, 2008
- An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cellsProceedings of the National Academy of Sciences, 2007
- Widespread deregulation of microRNA expression in human prostate cancerOncogene, 2007
- Muscle-specific microRNA miR-206 promotes muscle differentiationThe Journal of cell biology, 2006
- MicroRNA expression profiles classify human cancersNature, 2005