Oncogene APOL1 promotes proliferation and inhibits apoptosis via activating NOTCH1 signaling pathway in pancreatic cancer

Cell Death Dis. 2021 Aug 2;12(8):760. doi: 10.1038/s41419-021-03985-1.

Abstract

APOL1 encodes a secreted high-density lipoprotein, which has been considered as an aberrantly expressed gene in multiple cancers. Nevertheless, the role of APOL1 in the regulatory mechanisms of pancreatic cancer remains unknown and should be explored. We identified APOL1 was abnormally elevated in human pancreatic cancer tissues compared with that in adjacent tissues and was associated with poor prognosis. The effects of APOL1 in PC cell proliferation, cell cycle, and apoptosis was verified via functional in vitro and in vivo experiments. The results showed that knockdown of APOL1 significantly inhibited the proliferation and promoted apoptosis of pancreatic cancer. In addition, we identified APOL1 could be a regulator of NOTCH1 signaling pathway using bioinformatics tools, qRT-PCR, dual-luciferase reporter assay, and western blotting. In summary, APOL1 could function as an oncogene to promote proliferation and inhibit apoptosis through activating NOTCH1 signaling pathway expression in pancreatic cancer; therefore, it may act as a novel therapeutic target for pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein L1 / metabolism*
  • Apoptosis* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Multivariate Analysis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Receptor, Notch1 / metabolism*
  • Signal Transduction*
  • Survival Analysis
  • Up-Regulation / genetics
  • Xenograft Model Antitumor Assays

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Receptor, Notch1