S100P acts as a target of miR-495 in pancreatic cancer through bioinformatics analysis and experimental verification

Kaohsiung J Med Sci. 2021 Jul;37(7):562-571. doi: 10.1002/kjm2.12383. Epub 2021 May 5.

Abstract

S100 calcium binding protein P (S100P) and miR-495 are aberrantly expressed and exert essential roles in cancers. However, the mechanisms of miR-495-S100P in pancreatic cancer are yet to be illustrated. Thus, we explored the regulatory functions of miR-495-S100P axis in pancreatic adenocarcinoma cells growth and invasion. In this study, we identified that S100P was upregulated in pancreatic adenocarcinoma by bioinformatics analysis of the GEO (Gene Expression Omnibus database) microarray dataset (GSE16515). Western blotting and luciferase reporter gene analysis exhibited that miR-495 negatively determined the level of S100P via binging to its 3'-untranslated regions (3'-UTRs). A series of functional experiments indicated that upregulation of miR-495 or S100P knockdown suppressed pancreatic adenocarcinoma cells proliferation, invasion, and promoted apoptosis. Furthermore, the expression of S100P was negatively associated with the level of miR-495 in The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma case-cohort. Besides, reintroduction of S100P debilitated the anti-cancer action of miR-495 in pancreatic adenocarcinoma cells. Our data indicated that miR-495 performed suppressive roles in pancreatic adenocarcinoma through targeting S100P.

Keywords: S100P; apoptosis; invasion; miRNA-495; pancreatic cancer.

MeSH terms

  • 3' Untranslated Regions
  • Adenocarcinoma / metabolism
  • Apoptosis
  • Calcium / metabolism
  • Calcium-Binding Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Computational Biology / methods
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • HEK293 Cells
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Protein Binding

Substances

  • 3' Untranslated Regions
  • Calcium-Binding Proteins
  • MIRN495 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • S100P protein, human
  • Calcium