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CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis.

Publication ,  Journal Article
Wu, J; Jiang, Z; Chen, C; Hu, Q; Fu, Z; Chen, J; Wang, Z; Wang, Q; Li, A; Marks, JR; Guo, C; Chen, Y; Zhou, J; Yang, L; Lin, C; Wang, S
Published in: Cancer Lett
August 28, 2018

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.

Duke Scholars

Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

August 28, 2018

Volume

430

Start / End Page

179 / 192

Location

Ireland

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • RNA, Small Interfering
  • RNA, Circular
  • RNA
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Neoplasm Invasiveness
  • Middle Aged
  • MicroRNAs
 

Citation

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Wu, J., Jiang, Z., Chen, C., Hu, Q., Fu, Z., Chen, J., … Wang, S. (2018). CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis. Cancer Lett, 430, 179–192. https://doi.org/10.1016/j.canlet.2018.05.033
Wu, Jie, Zerun Jiang, Chen Chen, Qingsong Hu, Ziyi Fu, Junjie Chen, Zhangding Wang, et al. “CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis.Cancer Lett 430 (August 28, 2018): 179–92. https://doi.org/10.1016/j.canlet.2018.05.033.
Wu J, Jiang Z, Chen C, Hu Q, Fu Z, Chen J, et al. CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis. Cancer Lett. 2018 Aug 28;430:179–92.
Wu, Jie, et al. “CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis.Cancer Lett, vol. 430, Aug. 2018, pp. 179–92. Pubmed, doi:10.1016/j.canlet.2018.05.033.
Wu J, Jiang Z, Chen C, Hu Q, Fu Z, Chen J, Wang Z, Wang Q, Li A, Marks JR, Guo C, Chen Y, Zhou J, Yang L, Lin C, Wang S. CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis. Cancer Lett. 2018 Aug 28;430:179–192.
Journal cover image

Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

August 28, 2018

Volume

430

Start / End Page

179 / 192

Location

Ireland

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • RNA, Small Interfering
  • RNA, Circular
  • RNA
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Neoplasm Invasiveness
  • Middle Aged
  • MicroRNAs