circTADA2As suppress breast cancer progression and metastasis via targeting miR-203a-3p/SOCS3 axis

Cell Death Dis. 2019 Feb 20;10(3):175. doi: 10.1038/s41419-019-1382-y.

Abstract

More and more evidence indicates that circular RNAs (circRNAs) have important roles in several diseases, especially in cancers. However, their involvement remains to be investigated in breast cancer. Through screening circRNA profile, we identified 235 differentially expressed circRNAs in breast cancer. Subsequently, we explored the clinical significance of two circTADA2As in a large cohort of triple-negative breast cancer (TNBC), and performed functional analysis of circTADA2A-E6 in vitro and in vivo to support clinical findings. Finally, we evaluated the effect of circTADA2A-E6 on miR-203a-3p and its target gene SOCS3. We detected two circRNAs, circTADA2A-E6 and circTADA2A-E5/E6, which were among the top five differentially expressed circRNAs in breast cancer. They were consistently and significantly decreased in a large cohort of breast cancer patients, and their downregulation was associated with poor patient survival for TNBC. Especially, circTADA2A-E6 suppressed in vitro cell proliferation, migration, invasion, and clonogenicity and possessed tumor-suppressor capability. circTADA2A-E6 preferentially acted as a miR-203a-3p sponge to restore the expression of miRNA target gene SOCS3, resulting in a less aggressive oncogenic phenotype. circTADA2As as promising prognostic biomarkers in TNBC patients, and therapeutic targeting of circTADA2As/miRNA/mRNA network may be a potential strategy for the treatment of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Lymphatic Metastasis
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Suppressor of Cytokine Signaling 3 Protein / genetics*
  • Suppressor of Cytokine Signaling 3 Protein / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transplantation, Heterologous
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology

Substances

  • DNA-Binding Proteins
  • MIRN203 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Small Interfering
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • TADA2A protein, human
  • Transcription Factors