Author/Editor		Hamilton, Mark Patrick; Rajapakshe, Kimal I.; Bader, David A; Černe, Jasmina Živa; Smith, Eric A.; Coarfa, Cristian; Hartig, Sean Michael; McGuire, Sean E.
Title		The landscape of microRNA targeting in prostate cancer defined by AGO-PAR-CLIP
Type		članek
Vol. and No.		Letnik 18, št. 6
Publication year		2016
Volume		str. 356-370
ISSN		1522-8002 - Neoplasia (New York, N.Y.)
Language		eng
Abstract		MicroRNA (miRNA) deregulation in prostate cancer (PCa) contributes to PCa initiation and metastatic progression. To comprehensively define the cancer-associated changes in miRNA targeting and function in commonly studied models of PCa, we performed photoactivatable ribonucleoside-enhanced cross-linking immunoprecipitation of the Argonaute protein in a panel of PCa cell lines modeling different stages of PCa progression. Using this comprehensive catalogue of miRNA targets, we analyzed miRNA targeting on known drivers of PCa and examined tissue-specific and stage-specific pathway targeting by miRNAs. We found that androgen receptor is the most frequently targeted PCa oncogene and that miR-148a targets the largest number of known PCa drivers. Globally, tissue-specific and stage-specific changes in miRNA targeting are driven by homeostatic response to active oncogenic pathways. Our findings indicate that, even in advanced PCa, the miRNA pool adapts to regulate continuing alterations in the cancer genome to balance oncogenic molecular changes. These findings are important because they are the first to globally characterize miRNA changes in PCa and demonstrate how the miRNA target spectrum responds to staged tumorigenesis.
Keywords		prostate cancer androgen receptor RNA molecules rak prostate androgeni receptor RNA molekule