CircAHNAK1 inhibits proliferation and metastasis of triple-negative breast cancer by modulating miR-421 and RASA1

Aging (Albany NY). 2019 Dec 19;11(24):12043-12056. doi: 10.18632/aging.102539. Epub 2019 Dec 19.

Abstract

Background: There is increasing evidence that circular RNAs (circRNAs) participate in regulating cancer progression. However, the function and potential molecular mechanisms of circRNA in triple negative breast cancer (TNBC) are currently largely unclear.

Results: We found that circAHNAK1 was significantly down-regulated in TNBC, and its expression was negatively associated with RFS and OS. Overexpression of circAHNAK1 can inhibit TNBC proliferation, migration and invasion in vitro. In vivo studies confirmed that circAHNAK1 inhibited TNBC tumor growth and metastasis. Mechanistic analysis indicated that circAHNAK1 acted as a miR-421 ceRNA (competitive endogenous RNA) to attenuate the inhibitory effect of miR-421 on its target gene RASA1.

Conclusions: In conclusion, CircAHNAK1 inhibits proliferation and metastasis of TNBC by modulating miR-421 and RASA1.

Methods: CircRNA microarrays were used to screen for differential circRNA expression profiles. qRT-PCR was used to detect the expression levels of circRNAs. The effect of circAHNAK1 on recurrence -free survival (RFS) and overall survival (OS) in patients with TNBC was subsequently analyzed. The role of circAHNKA1 in the progression of TNBC was further evaluated by multiple in vivo and in vitro assays. Finally, we focused on the regulation of circAHNAK1 on miR-421 and its targeted gene RASA1 in TNBC.

Keywords: RASA1; biomarker; circAHNAK1; miR-421; triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Proteins / genetics*
  • RNA, Circular / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • p120 GTPase Activating Protein / genetics*

Substances

  • AHNAK protein, human
  • MIRN421 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • RASA1 protein, human
  • RNA, Circular
  • p120 GTPase Activating Protein