Long non-coding RNA FGF13-AS1 inhibits glycolysis and stemness properties of breast cancer cells through FGF13-AS1/IGF2BPs/Myc feedback loop

Cancer Lett. 2019 May 28:450:63-75. doi: 10.1016/j.canlet.2019.02.008. Epub 2019 Feb 14.

Abstract

LncRNAs have been proven to play crucial roles in various processes of breast cancer. LncRNA FGF13-AS1 has been identified as one of the 25 downregulated lncRNAs in breast cancer through analyzing data from two cohorts and TCGA by another group of our lab. In this study, we report that FGF13-AS1 expression is decreased in breast cancer tissue compared with corresponding normal tissue, and the downregulation of FGF13-AS1 is associated with poor prognosis. Functional studies show that FGF13-AS1 inhibits breast cancer cells proliferation, migration, and invasion by impairing glycolysis and stemness properties. Mechanistically, FGF13-AS1 reduces the half-life of c-Myc (Myc) mRNA by binding RNA-binding proteins, insulin-like growth factor 2 mRNA binding proteins (IGF2BPs) and disrupting the interaction between IGF2BPs and Myc mRNA. Furthermore, Myc transcriptionally inhibits FGF13-AS1, forming a feedback loop in this signaling pathway. These results reveal for the first time that FGF13-AS1 functions as a tumor suppressor by inhibiting glycolysis and stemness properties of breast cancer cells, and the FGF13-AS1/IGF2BPs/Myc feedback loop could be a novel therapeutic target for breast cancer patients.

Keywords: Lnc FGF13-AS1; Metabolism; Stemness; c-Myc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • Feedback, Physiological
  • Female
  • Fibroblast Growth Factors
  • Glycolysis
  • Heterografts
  • Humans
  • Insulin-Like Growth Factor II / metabolism
  • MCF-7 Cells
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Oligoribonucleotides, Antisense
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction

Substances

  • IGF2BP1 protein, human
  • IGF2BP2 protein, human
  • IGF2BP3 protein, human
  • MYC protein, human
  • Oligoribonucleotides, Antisense
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • fibroblast growth factor 13
  • Fibroblast Growth Factors
  • Insulin-Like Growth Factor II