LINC00525 enhances ZNF460-regulated CD24 expression through the sponge miR-125a-5p to promote malignant progression of breast cancer

J Cancer Res Clin Oncol. 2024 Jun 24;150(6):317. doi: 10.1007/s00432-024-05830-2.

Abstract

Introduction: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer.

Methodology: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting.

Results: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression.

Conclusions: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.

Keywords: CD24; LINC00525; Migration; Proliferation; ZNF460; miR-125a-5p.

MeSH terms

  • Animals
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • CD24 Antigen* / genetics
  • CD24 Antigen* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation*
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs* / genetics
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • CD24 Antigen
  • MicroRNAs
  • CD24 protein, human
  • MIRN125 microRNA, human
  • RNA, Long Noncoding
  • Transcription Factors