MicroRNA-448 targets SATB1 to reverse the cisplatin resistance in lung cancer via mediating Wnt/β-catenin signalling pathway

J Biochem. 2020 Jul 1;168(1):41-51. doi: 10.1093/jb/mvaa024.


This study aims to examine whether miR-448 reverses the cisplatin (DDP) resistance in lung cancer by modulating SATB1. QRT-PCR and immunohistochemistry were used to examine the miR-448 and SATB1 expressions in DDP-sensitive and -resistant lung cancer patients. A microarray was used to investigate the cytoplasmic/nucleic ratio (C/N ratios) of genes in A549 cells targeted by miR-448, followed by Dual-luciferase reporter gene assay. A549/DDP cells were transfected with miR-448 mimics/inhibitors with or without SATB1 siRNA followed by MTT assay, Edu staining, flow cytometry, qRT-PCR and western blotting. MiR-448 was lower but SATB1 was increased in DDP-resistant patients and A549/DDP cells. And the patients showed low miR-448 expression or SATB1 positive expression had poor prognosis. SATB1, as a target gene with higher C/N ratios (>1), was found negatively regulated by miR-448. Besides, miR-448 inhibitors increased resistance index of A549/DDP cells, promoted cell proliferation, increased cell distribution in S phrase, declined cell apoptosis and activated Wnt/β-catenin pathway. However, SATB1 siRNA could reverse the above effect caused by miR-448 inhibitors. MiR-448 targeting SATB1 to counteract the DDP resistance of lung cancer cells via Wnt/β-catenin pathway.

Keywords: SATB1; cisplatin; drug resistance; lung cancer; miR-448.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • MicroRNAs / genetics*
  • Survival Rate
  • Wnt Signaling Pathway*


  • Antineoplastic Agents
  • MIRN448 microRNA, human
  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • SATB1 protein, human
  • Cisplatin