Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression

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.

Mucin 1 Aberrantly Expresses in Goat Mammary Carcinoma

“…FNDC3B is mammary stem cell and cancer cell marker reported by many investigators. [23][24][25][26][27][28] Our earlier report of increased expression of FNDC3B in buffalo mammary cancer 24 was consistent with the present finding of goat mammary cancer. Cyclin B1 (CCNB1) is a cell cycle protein in G2/M transition.…”

TGF-β1 acts through miR-155 to down-regulate TP53INP1 in promoting epithelial–mesenchymal transition and cancer stem cell phenotypes

“…Several studies demonstrated that serum-free culture medium is an effective method to enrich and identify CSCs [32,44,45]. Therefore, we used this method to enrich for liver cancer stem cells, and collected many spheres.…”

Diversity and functional convergence of small noncoding RNAs in male germ cell differentiation and fertilization

“…Analyzing the miRNA population of spermatozoa, we found that the vast majority of miRNAs accumulated in spermatozoa were also detected in spermatogonia cells but showing different expression levels (Supplemental Table 1). For example, one of them, the miR-143-3p, that has been reported as involved in cell proliferation and differentiation (Huang et al 2012;Fan et al 2013), was the highest accumulated in spermatozoa being also the most abundant in spermatogonia cells. This miRNA was detected in all cell types, but especially in spermatogonia cells and spermatozoa (Supplemental Table 1).…”