MicroRNA-383 located in frequently deleted chromosomal locus 8p22 regulates CD44 in prostate cancer.

A major genomic alteration in prostate cancer (PCa) is frequent loss of chromosome (chr) 8p with a common region of loss of heterozygosity (LOH) at chr8p22 locus. Genomic studies implicate this locus in the initiation of clinically significant PCa and with progression to metastatic disease. However, the genes within this region have not been fully characterized to date. Here we demonstrate for the first time that a microRNA component of this region-miR-383-is frequently downregulated in prostate cancer, has a critical role in determining tumor-initiating potential and is involved in prostate cancer metastasis via direct regulation of CD44, a ubiquitous marker of PCa tumor-initiating cells (TICs)/stem cells. Expression analyses of miR-383 in PCa clinical tissues established that low miR-383 expression is associated with poor prognosis. Functional data suggest that miR-383 regulates PCa tumor-initiating/stem-like cells via CD44 regulation. Ectopic expression of miR-383 inhibited tumor-initiating capacity of CD44+ PCa cells. Also, 'anti-metastatic' effects of ectopic miR-383 expression were observed in a PCa experimental metastasis model. In view of our results, we propose that frequent loss of miR-383 at chr8p22 region leads to tumor initiation and prostate cancer metastasis. Thus, we have identified a novel finding that associates a long observed genomic alteration to PCa stemness and metastasis. Our data suggest that restoration of miR-383 expression may be an effective therapeutic modality against PCa. Importantly, we identified miR-383 as a novel PCa tissue diagnostic biomarker with a potential that outperforms that of serum PSA

Oncogenic miRNA-182-5p Targets Smad4 and RECK in Human Bladder Cancer

Onco-miR-182-5p has been reported to be over-expressed in bladder cancer (BC) tissues however a detailed functional analysis of miR-182-5p has not been carried out in BC. Therefore the purpose of this study was to: 1. conduct a functional analysis of miR-

Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells

Background:Wnt-signalling has an important role in renal cancer and it is modulated by genistein in other cancers. Recently, microRNAs (miRNAs) have emerged as new regulators of gene expression. Thus, we focused on miRNAs to examine the regulatory mechani

Oncogenic miRNA-182-5p Targets Smad4 and RECK in Human Bladder Cancer

Onco-miR-182-5p has been reported to be over-expressed in bladder cancer (BC) tissues however a detailed functional analysis of miR-182-5p has not been carried out in BC. Therefore the purpose of this study was to: 1. conduct a functional analysis of miR-

Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells

Background: Recently several microRNAs (miRNAs) have been found to be regulated by genistein in cancer cells. In this study, we focused on the gene regulatory effect of genistein on microRNA and its target genes in prostate cancer (PC). Methods: Initially

MicroRNA-182-5p Promotes Cell Invasion and Proliferation by Down Regulating FOXF2, RECK and MTSS1 Genes in Human Prostate Cancer

Recently miR-182 has been reported to be over-expressed in prostate cancer (PC) tissues, however detailed functional analysis of miR-182-5p has not been carried out. The purpose of this study was to: 1. analyze the function of miR-182-5p in prostate cance

MicroRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer

Background: The purpose of this study was to identify prostate cancer (PC) oncogenic microRNAs (miRs) based on miR microarray and to investigate whether these oncogenic miRs may be useful as PC biomarkers.Methods:Initially, we carried out miR microarray a

MicroRNA-182-5p Promotes Cell Invasion and Proliferation by Down Regulating FOXF2, RECK and MTSS1 Genes in Human Prostate Cancer

Recently miR-182 has been reported to be over-expressed in prostate cancer (PC) tissues, however detailed functional analysis of miR-182-5p has not been carried out. The purpose of this study was to: 1. analyze the function of miR-182-5p in prostate cance