Inhibition of miR-194 suppresses the Wnt/β-catenin signalling pathway in gastric cancer

Yin Peng, Xiaojing Zhang, Huijuan Lin, Shiqi Deng, Yong Huang, Ying Qin, Xianling Feng, Ruibin Yan, Yanqiu Zhao, Yulan Cheng, Yanjie Wei, Jian Wang, Wangchun Chen, Xinmin Fan, Hassan Ashktorab, Duane Smoot, Stephen J. Meltzer, Song Li, Zhong Zhang, Zhe Jin

Research output: Contribution to journalArticlepeer-review

Abstract

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/β-catenin signalling is positively associated with human malignancy. In addition, miR.194 dysregulation has been implicated in gastric cancer (GC); however, the molecular mechanisms underlying the effects of miR-194 on GC carcinogenesis remain to be elucidated. The present study demonstrated that miR-194 was upregulated in GC tissues and SUFU negative regulator of hedgehog signaling (SUFU) was downregulated in GC cell lines. Subsequently, inhibition of miR-194 attenuated nuclear accumulation of β-catenin, which consequently blocked Wnt/β-catenin signalling. In addition, the cytoplasmic translocation of β-catenin induced by miR-194 inhibition was mediated by SUFU. Furthermore, genes associated with the Wnt/β-catenin signalling pathway were revealed to be downregulated following inhibition of the Wnt signalling pathway by miR-194 suppression. Finally, the results indicated that cell apoptosis was markedly increased in response to miR-194 inhibition, strongly suggesting the carcinogenic effects of miR-194 in GC. Taken together, these findings demonstrated that miR-194 may promote gastric carcinogenesis through activation of the Wnt/β-catenin signalling pathway, making it a potential therapeutic target for GC.

Original languageEnglish (US)
Pages (from-to)3323-3334
Number of pages12
JournalOncology reports
Volume40
Issue number6
DOIs
StatePublished - Dec 2018

Keywords

  • Apoptosis
  • MicroRNA-194
  • SUFU negative regulator of hedgehog signaling
  • Wnt/β-catenin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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