Abstract
BackgroundRecent data show aberrant and altered expression of regulatory noncoding micro (mi) RNAs in prostate cancer (PCa). A large number of miRNAs are encoded in organized intronic clusters within many protein coding genes. While expression profiling studies of miRNAs are common place, little is known about the host gene and their resident miRNAs coordinated expression in PCa cells. Furthermore, whether expression of a subset of miRNAs is distinct in androgen-responsive and androgen-independent cells is not clear. Here we have examined the expression of mature miRNAs of miR 17–92, miR 106b-25 and miR 23b-24 clusters along with their host genes C13orf25, MCM7 and AMPO respectively in PCa cell lines.ResultsThe expression profiling of miRNAs and host genes was performed in androgen-sensitive MDA PCa 2b and LNCaP as well as in androgen-refractory PC-3 and DU 145 cell culture models of PCa. No significant correlation between the miRNA expression and the intrinsic hormone-responsive property of PCa cells was observed. Androgen-sensitive MDA PCa 2b cells exhibited the highest level of expression of most miRNAs studied in this report. We found significant expression variations between host genes and their resident miRNAs. The expressions of C13orf25 and miR 17–92 cluster as well as MCM7 and miR 106b-25 cluster did not reveal statistically significant correlation, thus suggesting that host genes and resident miRNAs may be expressed independent of each other.ConclusionOur results suggest that miRNA expression profiles may not predict intrinsic hormone-sensitive environment of PCa cells. More importantly, our data indicate the possibility of additional novel mechanisms for intronic miRNA processing in PCa cells.
Highlights
Recent data show aberrant and altered expression of regulatory noncoding micro RNAs in prostate cancer (PCa)
Regulatory noncoding microRNAs play a critical role in the regulation of gene expression [5] and are potential candidates for studying their role in the progression of PCa to androgen-independent stage. Maintenance; (ORF): Open Reading Frame; (miRNA) control gene expression by binding to the complementary sites in the 3' untranslated regions (3' UTRs) of target mRNAs and triggering either translational inhibition or mRNA degradation by a molecular mechanism which is a subject of intense investigation [6,7,8,9]
Expression Profiling of miR 17–92, 106b-25 and 23b-24 Clusters in Androgen-Dependent and AndrogenRefractory PCa Cell Lines by Northern Blotting Two distinct stages of PCa are recapitulated in a variety of human PCa cell culture models
Summary
Recent data show aberrant and altered expression of regulatory noncoding micro (mi) RNAs in prostate cancer (PCa). Regulatory noncoding microRNAs (miRNAs) play a critical role in the regulation of gene expression [5] and are potential candidates for studying their role in the progression of PCa to androgen-independent stage. Recent studies have demonstrated the aberrant expression of miRNAs in PCa tissues and cell lines [30,31,32,33,34] and differential expression of a miRNA in androgendependent and androgen-independent PCa cells [29]. Androgen-regulated miRNAs may play a role in the transition of PCa to the androgen-independent stage [35]. The role of miRNAs and their differential signature expression patterns in androgen-dependent and androgen-independent PCa cells requires a closer validation
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