SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer

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

Research output: Contribution to journalArticlepeer-review

Abstract

The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/β-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressed in vivo and exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer.

Original languageEnglish (US)
Pages (from-to)2720-2733
Number of pages14
JournalCell Cycle
Volume19
Issue number20
DOIs
StatePublished - Oct 17 2020

Keywords

  • EMT
  • SUFU negative regulator of hedgehog signaling
  • Wnt/β-catenin
  • miRNA-324-5p

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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