Hsa_circ_0069094 accelerates cell malignancy and glycolysis through regulating the miR-591/HK2 axis in breast cancer

Cell Signal. 2021 Mar:79:109878. doi: 10.1016/j.cellsig.2020.109878. Epub 2020 Dec 9.

Abstract

Circular RNAs (circRNAs) are implicated in the initiation and advancement of diverse tumors. CircRNA hsa_circ_0069094 (circ_0069094) has been reported to be upregulated in BC, but the biological role of circ_0069094 in BC is indistinct. Hence, we aimed to survey the biological role of circ_0069094 in BC. In the present study, we verified that circ_0069094 was upregulated in BC tissues and cells. BC patients with high circ_0069094 expression had a poor prognosis. Functional analysis revealed that circ_0069094 silencing induced apoptosis, curbed proliferation, and reduced glycolysis in BC cells in vitro, but circ_0069094 overexpression had an opposing influence. Also, circ_0069094 knockdown reduced BC growth in vivo. Mechanically, circ_0069094 was validated as a decoy for miR-591, which targeted HK2. Importantly, circ_0069094 sponged miR-591 to regulate HK2 expression. Both miR-591 silencing and HK2 overexpression counteracted circ_0069094 inhibition-mediated influence on cell proliferation, apoptosis, and glycolysis in BC cells. In conclusion, these results indicated that circ_0069094 facilitated cell malignancy and glycolysis by upregulating HK2 through adsorbing miR-591, suggesting that circ_0069094 might be a prognostic biomarker and therapeutic target for BC.

Keywords: BC; Glycolysis; HK2; circ_0069094; miR-591.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Glycolysis*
  • Hexokinase / genetics
  • Hexokinase / metabolism*
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*

Substances

  • MIRN591 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Circular
  • RNA, Neoplasm
  • HK2 protein, human
  • Hexokinase