Abstract
BackgroundMetastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells.MethodsA microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143.ResultsThe expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo.ConclusionsThese data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer.
Highlights
Metastatic prostate cancer is a leading cause of cancer-related death in men
MiR-143 expression was progressively increased during PC-3 sphere cells differentiation First, to elucidate whether the PC-3 sphere cells turned into differentiated cells when sphere cells were digested
We selected miR-143 to further investigate its role in prostate cancer. These results suggested that miR-143 might play a regulatory role in prostate cancer stem cells differentiation in vitro
Summary
Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells. Prostate cancer is the most frequently diagnosed malignant disease in men and the second leading cause of cancer deaths in US [1]. Most patients eventually relapse with castration-resistant prostate cancer and develop metastatic disease, which has a poor prognosis. CSCs are thought to be responsible for tumor initiation, progression, therapy resistance, relapse and metastasis [3]. The role of prostate cancer stem cells in tumor development and metastasis is still poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
