miR-21-5p promotes lung adenocarcinoma progression partially through targeting SET/TAF-Iα

Life Sci. 2019 Aug 15:231:116539. doi: 10.1016/j.lfs.2019.06.014. Epub 2019 Jun 6.

Abstract

Objective: Although SET(I2PP2A) and miRNAs are reported to play a pivotal role in lung cancer, the underlying mechanisms have remained obscure. To address this issue, we investigated how miRNAs and SET participate in the progression of lung cancer.

Methods: miRNAs that target SET were predicted from multiple miRNA databases. Three human NSCLC cell lines and two normal lung cell lines were used to evaluate aberrant miRNA and SET expressions. A dual luciferase reporter assay system was employed to verify the interaction between miRNA and SET. Stable miRNA knockdown and SET overexpression in A549 cells were achieved through lentivirus transfection; the corresponding influences on lung cancer progression were also examined.

Results: In this study, A549 was the sole cell line to lack SET/TAF-Iα expression, which was inversely correlated with the up-regulation of miR-21-5p. SET was subsequently revealed as the direct target site of miR-21-5p in A549 cells. The stable miR-21-5p knockdown and SET/TAF-Iα overexpression were shown to markedly enhance the expression of SET/TAF-Iα and to inhibit the migration, invasion, proliferation as well as the in vivo tumorigenicity of A549 cells.

Conclusion: We suggest that SET/TAF-Iα might be a tumor suppressing factor regulated by miR-21-5p in lung adenocarcinoma. This might provide a target for lung adenocarcinoma therapy.

Keywords: Lung adenocarcinoma; SET/TAF-Iα; miR-21-5p.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / pathology
  • Animals
  • Apoptosis / physiology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • DNA-Binding Proteins
  • Disease Progression
  • Female
  • Histone Chaperones / metabolism*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Histone Chaperones
  • MIRN21 microRNA, human
  • MicroRNAs
  • SET protein, human
  • Transcription Factors