MicroRNA-21 regulates the ERK/NF-κB signaling pathway to affect the proliferation, migration, and apoptosis of human melanoma A375 cells by targeting SPRY1, PDCD4, and PTEN

Mol Carcinog. 2017 Mar;56(3):886-894. doi: 10.1002/mc.22542. Epub 2016 Sep 22.


This study aims to explore the effects of microRNA-21 (miR-21) and ERK/NF-κB signaling pathway on human melanoma A375 cells. The melanoma tissues and adjacent normal tissues were obtained from 45 melanoma patients. qRT-PCR was conducted to quantify the expression of miR-21 and the gene mRNA expressions. Human melanoma A375 cells were divided into the Mock, negative control (NC), miR-21 inhibitors, miR-21 inhibitors + siRNA-SPRY1, miR-21 inhibitors + siRNA-PDCD4, and miR-21 inhibitors + siRNA-PTEN groups. Western blotting was used to determine protein expressions. CCK8 assay and Transwell assay were performed to evaluate the proliferation, migration, and invasion of A375 cells. Annexin V/propidium iodide double staining was adopted to detect cell apoptosis. MiR-21 expression was higher in melanoma tissues than in adjacent tissues, while the mRNA and protein expressions of SPRY1, PDCD4, and PTEN were lower in melanoma tissues than in adjacent tissues. Compared with the Mock and NC groups, the miR-21 inhibitors group exhibited increased expressions of SPRY1, PDCD4, and PTEN and decreased expressions of ERK, p-ERK, NF-κB p65, and p-NF-κB p65. After transfection of miR-21 inhibitors, the proliferation, migration, and invasion of A375 cells were inhibited, while the apoptosis of A375 cells was promoted. However, the effects of miR-21 inhibitors on the growth, migration, invasion, and apoptosis of A375 cells were reversed after transfection of siRNA-SPRY1, siRNA-PDCD4, or siRNA-PTEN. MiR-21 can promote the proliferation, migration, and inhibit the apoptosis of human melanoma A375 cells by inhibiting SPRY1, PDCD4, and PTEN via ERK/NF-κB signaling pathway. © 2016 Wiley Periodicals, Inc.

Keywords: ERK/NF-κB signaling pathway; PDCD4; PTEN; SPRY1; melanoma; microRNA-21.

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*


  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • MIRN21 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • NF-kappa B
  • PDCD4 protein, human
  • Phosphoproteins
  • RNA-Binding Proteins
  • SPRY1 protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human