MicroRNA-7 inhibits the malignant phenotypes of non‑small cell lung cancer in vitro by targeting Pax6

Mol Med Rep. 2015 Oct;12(4):5443-8. doi: 10.3892/mmr.2015.4032. Epub 2015 Jul 2.

Abstract

MicroRNA (miR)-7 has been reported to act as a suppressor in several types of cancer, including non-small cell lung cancer (NSCLC). In addition, paired box 6 (Pax6), a highly conserved transcriptional factor, has been implicated in NSCLC. However, the exact role of miR-7, and the association between miR-7 and Pax6 in NSCLC cells remain to be fully elucidated. The present study demonstrated that miR-7 was downregulated and Pax6 was upregulated in NSCLC cell lines. Subsequently, it was demonstrated that overexpression of miR-7 notably inhibited the protein expression of Pax6, while inhibition of miR-7 enhanced the protein expression of Pax6 in NSCLC A549 cells. Further investigation identified Pax6 as a target of miR-7 in A549 NSCLC cells. Ina ddition, the overexpression of miR-7 significantly inhibited A549 cell proliferation and invasion, which was reversed by upregulation of Pax6. Investigation of the underlying molecular mechanism revealed that the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways were downregulated in the miR-7-overexpressed A549 cells, but were activated in the Pax6-overexpressed A549 cells. Based on these findings, it was suggested that miR-7 negatively regulates the protein level of Pax6, which can promote the proliferation and invasion of NSCLC cells via activation of the ERK and MAPK signaling pathways. Therefore, miR-7/Pax6 may offer potential for use as a target for the treatment of NSCLC.

Publication types

  • Retracted Publication

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • MicroRNAs / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics*
  • Paired Box Transcription Factors / metabolism
  • Phenotype
  • RNA Interference*
  • RNA, Messenger / genetics
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Eye Proteins
  • Homeodomain Proteins
  • MIRN7 microRNA, human
  • MicroRNAs
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • RNA, Messenger
  • Repressor Proteins
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases