Long non-coding RNA DLEU1 promotes malignancy of breast cancer by acting as an indispensable coactivator for HIF-1α-induced transcription of CKAP2

Cell Death Dis. 2022 Jul 19;13(7):625. doi: 10.1038/s41419-022-04880-z.

Abstract

Earlier studies have suggested deleted in lymphocytic leukemia 1 (DLEU1), a long non-coding RNA, is a prognostic biomarker for breast cancer. Here we explored the malignant behaviors and underlying mechanisms regulated by DLEU1 in breast cancer. We demonstrated that up-regulation of DLEU1 was detected in breast cancer tissues and cells, particularly in tumors of higher malignancy. DLEU1 knockdown inhibited the growth and the motility of breast cancer cells. Mechanistically, DLEU1 interacted with HIF-1α to collectively activate the transcription of CKAP2. By activating ERK and STAT3 signaling, CKAP2 essentially mediated the pro-tumor activities of DLEU1. In vivo, depletion of DLEU1 inhibited xenograft growth and metastasis of breast cancer cells. Therefore, DLEU1, by acting as a coactivator for HIF-1α, up-regulates CKAP2 expression and promotes malignancy of breast cancer. Targeting DLEU1, HIF-1α, or CKAP2 may thus benefit breast cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cytoskeletal Proteins* / genetics
  • Cytoskeletal Proteins* / metabolism
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Transcriptional Activation
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • CKAP2 protein, human
  • Cytoskeletal Proteins
  • DLEU1 lncRNA, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins