[No authors listed]
A mounting body of evidence has revealed that microRNAs (miRs) serve pivotal roles in various developmental processes, and in tumourigenesis, by binding to target genes and subsequently regulating gene expression. Continued activation of the Wnt/βâcatenin signalling is positively associated with human malignancy. In addition, miRâ194 dysregulation has been implicated in gastric cancer (GC); however, the molecular mechanisms underlying the effects of miRâ194 on GC carcinogenesis remain to be elucidated. The present study demonstrated that miRâ194 was upregulated in GC tissues and SUFU negative regulator of Îedgehog signaling (SUFU) was downregulated in GC cell lines. Subsequently, inhibition of miRâ194 attenuated nuclear accumulation of βâcatenin, which consequently blocked Wnt/βâcatenin signalling. In addition, the cytoplasmic translocation of βâcatenin induced by miRâ194 inhibition was mediated by SUFU. Furthermore, genes associated with the Wnt/βâcatenin signalling pathway were revealed to be downregulated following inhibition of the Wnt signalling pathway by miRâ194 suppression. Finally, the results indicated that cell apoptosis was markedly increased in response to miRâ194 inhibition, strongly suggesting the carcinogenic effects of miRâ194 in GC. Taken together, these findings demonstrated that miRâ194 may promote gastric carcinogenesis through activation of the Wnt/βâcatenin signalling pathway, making it a potential therapeutic target for GC.
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