Prostate cancer is the most frequently diagnosed malignant disease in men and the second leading cause of cancer deaths in US . The treatment of prostate cancer with surgical resection, which may be combined with chemotherapy, hormone therapy or radiation therapy, is curative in many patients. However, most patients eventually relapse with castration-resistant prostate cancer and develop metastatic disease, which has a poor prognosis because no effective treatments are currently available . Although basic knowledge related to metastasis has increased recently, many of the key elements remain largely unknown.
Cancer stem cells (CSCs), a small subpopulation of cells in a tumor, can self-renew and differentiate into multiple lineages, and they possess strong tumor-initiating capacity. Therefore, CSCs are thought to be responsible for tumor initiation, progression, therapy resistance, relapse and metastasis . Accumulating evidence has demonstrated the existence of prostate cancer stem cells, which can be been enriched by sorting for CD44+/CD133+ expression [4, 5] or by selecting cells that have the capacity to exclude Hoechst dye  or form spheres in serum-free suspension culture [7, 8]. However, the role of prostate cancer stem cells in tumor development and metastasis is still poorly understood.
MicroRNAs (miRNAs) are small, noncoding RNAs of approximately 19 to 25 nucleotides in length that usually bind to the 3′-untranslated region (UTR) of their mRNA targets, resulting in degradation or translation repression . Emerging evidence shows that the dysregulation of miRNAs is involved in cancer proliferation, differentiation, apoptosis and metastasis, and miRNAs function as oncogenes or tumor suppressors . In addition, miRNAs have emerged as important regulators of CSCs. Yu and colleagues discovered that let-7 regulates breast tumor-initiating cells properties by silencing genes involved in self-renewal and differentiation . A recent study has revealed that miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44 . It was demonstrated that miR-320 suppresses the stem cell-like characteristics of prostate cancer cells by down-regulating the Wnt/beta-catenin signaling pathway .
A series of miRNAs has been identified to be up-regulated in prostate cancer, including miR-21, miR-24, miR-32, miR-125b, and miR-221/222. Conversely, miR-7, miR-34a, miR-101, miR-143/145, and let-7a have been identified to be down-regulated in prostate cancer . Furthermore, several miRNAs have been identified as mediators of metastasis in prostate cancer. It was demonstrated that miR-221 was progressively reduced in aggressive and metastasis prostate cancer and predicted clinical recurrence . A previous study revealed that miR-21 was overexpressed in prostate cancer and promoted apoptotic resistance, invasion and metastasis by targeting MARCKS . A recent study has shown that miR-143 plays an important role in prostate cancer proliferation, migration and chemosensitivity by suppressing KRAS . More recently, miR-29b was identified as an anti-metastatic miRNA for prostate cancer cells by regulating epithelial–mesenchymal transition (EMT) signaling . However, the role of miRNAs in prostate cancer stem cells and metastasis remains to be elucidated.
In our previous study, we enriched and characterized prostate cancer stem cells from PC-3 sphere cells in a defined serum-free medium . In this paper, we use spheres as a prostate cancer stem cells model to elucidate the role of miRNAs in prostate cancer metastasis. In this study, we compared the miRNA expression profiles of PC-3 spheres and adherent cells of prostate cancer and identified that miR-143 was related to CSCs and metastasis. Moreover, we demonstrated that the down-regulation of miR-143 suppressed migration and invasion in vitro and tumor metastasis in vivo.