Upregulation of circ-UBAP2 predicts poor prognosis and promotes triple-negative breast cancer progression through the miR-661/MTA1 pathway

Biochem Biophys Res Commun. 2018 Nov 10;505(4):996-1002. doi: 10.1016/j.bbrc.2018.10.026. Epub 2018 Oct 9.

Abstract

Recently, a large number of studies have shown that circular RNA (circRNA) is involved in the development and progression of human cancer. However, its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, a novel circRNA, circ-UBAP2 (hsa_circ_0001846), was shown to be markedly upregulated in TNBC. Moreover, high circ-UBAP2 expression was closely associated with larger tumour size (p = 0.003), advanced TNM stage (p = 0.005), lymph node metastasis (p = 0.002), and unfavourable prognosis (p = 0.0256). Functionally, lentivirus-mediated stable knockdown of circ-UBAP2 dramatically weakened the ability of TNBC cells to proliferate and migrate and induced apoptosis in vitro and in vivo. Regarding the mechanism, we found that circ-UBAP2 was mainly observed in the cytoplasm and was capable of sponging miRNA-661 to increase the expression of the oncogene MTA1. Additionally, silencing of miRNA-661 or overexpression of MTA1 could partially rescue the attenuated malignant phenotype caused by circ-UBAP2 knockdown. Taken together, our data reveal that circ-UBAP2 plays a vital regulatory role in TNBC via the miR-661/MTA1 axis and may serve as a promising therapeutic target for TNBC patients.

Keywords: Prognosis; Progression; TNBC; circ-UBAP2; circRNA.

MeSH terms

  • Animals
  • Female
  • Histone Deacetylases / metabolism*
  • Humans
  • Mammary Neoplasms, Experimental / diagnosis
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • RNA / metabolism*
  • RNA, Circular
  • Repressor Proteins / metabolism*
  • Trans-Activators
  • Triple Negative Breast Neoplasms / diagnosis*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Cells, Cultured
  • Up-Regulation*

Substances

  • MIRN661 microRNA, human
  • MicroRNAs
  • MTA1 protein, human
  • RNA, Circular
  • Repressor Proteins
  • Trans-Activators
  • RNA
  • Histone Deacetylases