miR-199a and miR-34c enhance the migration of prostate cancer stem cells but inhibit migration of PC3 prostate cancer cells

Cancer stem cells (CSCs) have been identified in several cancers, including prostate cancer (PCa). Although prostate cancer stem cells (PCSCs) may differentiate into the various cells that constitute the PCa tumor, PCSC biology is markedly distinct from that of the PCa tumor mass. Delineating these differences could hold the key to understanding PCa progression, including epithelial-to-mesenchymal transition (EMT) and metastasis. Because CSCs are modulated by microRNAs (miRNAs), which may influence resistance to treatment and metastasis, we investigated the differential expression of miRNAs in PCSCs and in PC3 cells and their effect on cell invasion and migration. We analyzed the miRNA expression profiles by microarray, and a subset was confirmed using qRT-PCR. Twenty-three miRNAs were differentially expressed of which seven were validated by qRT-PCR, including has-miR199a, has-miR155, let-7d, has-miR34b, has-miR-34c, has-miR-505, and has-miR-196a. We then selected two miRNAs, miR-199a and miR-34c, that were highly expressed in PCSCs, and investigated their effect on PCSC invasion and migration using Matrigel invasion assays and scratch wound assays, respectively. Neither miR-199a nor miR-34c inhibition altered PCSC or PC3 cell invasion; however, inhibition of miR-199aor miR-34c reduced PCSC migration and enhanced PC3 cell migration. The effects of miR-199a and miR-34c inhibition on PCSC and PC3 cell migration suggest they may represent potential biomarkers and therapeutic targets in the treatment of PCa, which requires validation in further studies.