Functional analysis of microRNAs in @entity1 XXXX stem cells.

@entity1 @entity650 @entity632 @entity4635 @entity522 @entity8111 @entity96 @entity5 @entity2857 @entity13058 @entity15893
MicroRNAs are endogenous small non-coding RNAs that regulate gene expression and @entity5 development. A rare population of @entity96 stem cells (HSCs) holds the extensive proliferative and self-renewal potential necessary to form a @entity96 . We postulated that specific transcriptional factors might regulate the expression of microRNAs and subsequently modulate the expression of gene products involved in phenotypic characteristics of HSCs. We evaluated the expression of microRNA in @entity1 HSCs by microarray profiling, and defined the target genes and functional effects of two groups of microRNA regulated by @entity650 and transcriptional factor Twist. A subset of highly chemoresistant and invasive HSCs was screened with aberrant expressions of cytokine @entity650 and Twist. We demonstrated that conserved let-7 and miR-181 family members were up-regulated in HSCs by global microarray-based microRNA profiling followed by validation with real-time polymerase chain reaction. Importantly, inhibition of let-7 increases the chemosensitivity of HSCs to @entity2857 and @entity632 whereas silencing of miR-181 led to a reduction in HSCs motility and invasion. Knocking down @entity650 and Twist in HSCs significantly reduced let-7 and miR-181 expression and subsequently inhibited chemoresistance and cell invasion. We showed that let-7 directly targets @entity4635 and @entity522 , whereas miR-181 directly targets @entity15893 , @entity8111 as well as @entity13058 ( @entity13058 ). In conclusion, alterations of @entity650 - and Twist-regulated microRNA expression in HSCs play a part in @entity5 spreading and responsiveness to chemotherapy. Our results define a novel regulatory mechanism of let-7/miR-181s suggesting that let-7 and miR-181 may be molecular targets for eradication of hepatocellular @entity5 .
