Circular RNA 000554 represses epithelial-mesenchymal transition in breast cancer by regulating microRNA-182/ZFP36 axis

FASEB J. 2020 Sep;34(9):11405-11420. doi: 10.1096/fj.201903047R. Epub 2020 Jul 30.

Abstract

Increasing evidence indicates that circular RNAs (circRNAs) play a crucial role in regulating microRNAs (miRs) and mRNAs during breast cancer (BC) progression. Based on the in silico analysis of circRNA/miR/mRNA in BC, we aim to define an important role of circRNA_000554 in BC in relation to miR-182 and zinc finger protein 36 (ZFP36). Low expression of circRNA_000554 and ZFP36, and high miR-182 expression were determined in the clinical BC tissues. CircRNA_000554 acted as a sponge of miR-182, and miR-182 directly targeted ZFP36. After that, in order to evaluate the effects of circRNA_000554, miR-182, and ZFP36 on cellular process, we evaluated in vitro epithelial-mesenchymal transition (EMT) and in vivo tumor growth after delivering a series of overexpression plasmids, mimic, inhibitor, or shRNAs into BC cells. Increasing circRNA_000554 suppressed EMT, cell invasion and migration during BC by depleting miR-182 and increasing ZFP36. The inhibitory effect of circRNA_000554 on tumor growth was validated in vivo. Taken together, the present study confirms that circRNA_000554 functioned as an inhibitor of EMT in BC and suggests a molecular mechanism that circRNA_000554 bound to miR-182 to upregulate ZFP36 in this process.

Keywords: ZFP36; breast cancer; circular RNA 000554; epithelial-to-mesenchymal transition; microRNA-182.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Circular / genetics*
  • Tristetraprolin / genetics*
  • Tristetraprolin / metabolism
  • Xenograft Model Antitumor Assays / methods

Substances

  • MicroRNAs
  • Mirn182 microRNA, human
  • RNA, Circular
  • Tristetraprolin
  • ZFP36 protein, human