Abstract
The major cause of mortality for prostate cancer (PCa) is metastasis; however, the metastatic mechanism remains unclear. MicroRNAs (miRNAs) alter the expression patterns of essential genes through posttranscriptional regulation during cancer development. The study was mainly aimed at identifying specific miRNA-messenger RNA (mRNA) interactions and signaling pathways associated with PCa distant metastasis. New analytical approaches were applied, combining miRNA and gene expression microarray, to screen differentially expressed miRNA-mRNA pairs in the normal prostate epithelial cell line RWPE-1, the highly-metastatic human PCa cell line PC-3M-1E8 (H-1E8 or 1E8) and the lowly metastatic cell line PC-3M-2B4 (L-2B4 or 2B4). Eight differentially expressed candidate miRNAs and their targets closely related to PCa metastasis were identified and validated in patients by using the Gene Expression Omnibus database. Among them, overexpression of hsa-miR-92b-3p and hsa-let-7a-5p and underexpression of their targets, such as glutathione-S-transferase M3 (GSTM3), baculoviral IAP repeat-containing 3, and cyclin-dependent kinase inhibitor 1 (CDKN1A), were also validated in H-1E8 cells compared with L-2B4 cells. Bioinformatics suggested that hsa-miR-92b-3p and hsa-let-7a-5p and their targets might promote PCa metastasis through platinum-based drug resistance and the JAK-STAT signaling pathway. H-1E8 and L-2B4 cells treated by cisplatin showed the greatly decreased levels of hsa-miR-92b-3p and hsa-let-7a-5p; however, in contrast to 2B4 cells, 1E8 cells did not negatively regulate the increase in the expression levels of the targets GSTM3 and CDKN1A. This finding suggests that the dysregulation between hsa-let-7a-5p/CDKN1A and hsa-miR-92b-3p/GSTM3 pairs is associated with platinum-based chemoresistance of metastatic cancer cells.