CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis

Jie Wu, Zerun Jiang, Chen Chen, Qingsong Hu, Ziyi Fu, Junjie Chen, Zhangding Wang, Qiang Wang, Aiping Li, Jeffrey R. Marks, Changying Guo, Yun Chen, Jianwei Zhou, Liuqing Yang, Chunru Lin, Shouyu Wang

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

As a class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified to regulate tumourigenesis and progression in multiple malignancies. However, the expression profiles and function of circRNAs in breast cancer metastasis are largely unknown. Here, we determined that the expression of a novel circRNA, which we named circIRAK3, was increased in metastatic breast cancer (BC) cells and predictive of BC recurrence. Gain-of-function and loss-of-function studies in BC cells demonstrated that circIRAK3 promoted cell migration, invasion and metastasis in vitro and in vivo but did not affect cell proliferation, colony formation or cell cycle progression. Using circIRAK3 in vivo precipitation and luciferase reporter assays, we identified miR-3607 as a circIRAK3-associated miRNA. Furthermore, RNA sequencing and bioinformatics analysis showed that forkhead box C1 (FOXC1), the target of miR-3607, was downregulated in circIRAK3-silenced cells and mediated circIRAK3-induced BC cell migration. Intriguingly, FOXC1 could, in turn, bind to the IRAK3 promoter, triggering a positive-feedback loop that perpetuated the circIRAK3/miR-3607/FOXC1 signaling axis. Collectively, our findings indicated that circIRAK3 may exert regulatory roles in BC metastasis and may be a potential target for metastatic BC therapy.

Original languageEnglish (US)
Pages (from-to)179-192
Number of pages14
JournalCancer Letters
Volume430
DOIs
StatePublished - Aug 28 2018

Keywords

  • Breast cancer
  • FOXC1
  • Metastasis
  • circRNA
  • miRNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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