The altered expression of MiR-221/-222 and MiR-23b/-27b is associated with the development of human castration resistant prostate cancer

Background: We have previously identified seven miRs-miR-221, -222, -23b, -27b, -15a, -16-1, and -203, that are differentially expressed in the hormone sensitive LNCaP cell line and the hormone resistant LNCaP-abl cell line and hypothesized that these miRs may characterize certain subtypes of human castration resistant prostate cancer (CRPC).

Methods: Functional studies in cell culture systems have been performed to determine the effect of alternated expression level on cellular response to androgen treatment. To determine the clinical relevance of the expression patterns of these miRs, we compared the expression levels of these seven miRs in normal prostate tissues from 86 individuals, prostate tumor tissues from 34 individuals with localized hormone naïve disease, and bone-derived metastatic CRPC tissues from 17 individuals.

Results: The altered expression of miR-221/-222 (as previously described) or miR-203 affected the cellular response to androgen treatment, suggesting their potential involvement in the transition to CRPC. However, the expression of miR-23b, -27b, -15a, and -16-1 did not have a significant influence in the cellular response to androgen treatment, suggesting that these miRs may not play a causative role in the CRPC phenotype. Comparison of the expression levels of these miRs in tissue samples revealed that strikingly, ∼90% of the analyzed metastatic CRPC tumors could be characterized by the increased miR-221/-222 expression and the down-regulated miR-23b/-27b expression.

Conclusions: This finding suggests that altered miR-221/-222 and miR-23b/-27b expression may be associated with the CRPC process.