KLF5-induced lncRNA IGFL2-AS1 promotes basal-like breast cancer cell growth and survival by upregulating the expression of IGFL1

Cancer Lett. 2021 Sep 1;515:49-62. doi: 10.1016/j.canlet.2021.04.016. Epub 2021 May 27.


Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer and has a poor prognosis. Kruppel-like factor 5 (KLF5) is an oncogenic transcription factor in BLBCs. The mechanism by which KLF5 promotes BLBC by regulating the transcription of lncRNAs has not been fully elucidated. In this study, we discovered that lncRNA IGFL2-AS1 is a downstream target gene of KLF5 and that IGFL2-AS1 mediates the pro-proliferation and pro-survival functions of KLF5. Additionally, we demonstrated that IGFL2-AS1 functions by upregulating the transcription of its neighboring gene IGFL1 via two independent mechanisms. On the one hand, nuclear IGFL2-AS1 promotes the formation of a KLF5/TEAD4 transcriptional complex at the IGFL1 gene enhancer. On the other hand, cytoplasmic IGFL2-AS1 inhibits the expression of miR4795-3p, which targets the IGFL1 gene. TNFα induces the expression of IGFL2-AS1 and IGFL1 through KLF5. Taken together, the results of this study indicate that IGFL2-AS1 and IGFL1 may serve as new therapeutic targets for BLBCs.

Keywords: BLBCs; TEAD4; TNFα; miR4795-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HEK293 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Kruppel-Like Transcription Factors / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Proteins / genetics*
  • RNA, Long Noncoding / genetics*
  • Transcription, Genetic / genetics
  • Transcriptional Activation / genetics
  • Up-Regulation / genetics*


  • IGFL1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • KLF5 protein, human
  • Kruppel-Like Transcription Factors
  • Neoplasm Proteins
  • RNA, Long Noncoding