Hsa-miR-217 Inhibits the Proliferation, Migration, and Invasion in Non-small Cell Lung Cancer Cells Via Targeting SIRT1 and P53/KAI1 Signaling

Balkan Med J. 2020 Jun 1;37(1):208-214. doi: 10.4274/balkanmedj.galenos.2020.2019.9.91. Epub 2020 Apr 9.


Background: Brain metastasis is a major cause of cancer death in patients with lung cancer. Sirtuin 1 and hsa-miR-217 have been identified to mediate the development of non-small cell lung cancer.

Aims: To investigate the roles of hsa-miR-217, its target sirtuin 1, and the P53/KAI1 axis in the brain metastasis from non-small cell lung cancer.

Study design: Cell culture study.

Methods: Human pulmonary adenocarcinoma brain metastasis cell line PC-14/B were incubated and treated with constructed lentiviral plasmids expressing miR-217 and/or sirtuin 1. BEAS-2B cell line was used as a control. The targeted regulation of miR-217 to sirtuin 1was examined using a dual-luciferase reporter assay. Cell proliferation, migration, invasion, and related protein expression were detected to examine the effect of the miR-217/sirtuin 1 expression on metastasis.

Results: PC-14/B cells expressed higher sirtuin 1 and lower P53 and KAI1 compared with BEAS-2B control cells (p<0.05). Sirtuin 1 was a direct target of miR-217. MiR-217 expression suppressed PC-14/B cell invasion (p=0.004), migration (p=0.001), and proliferation (p<0.05), whereas sirtuin 1 overexpression reversed all processes. sirtuin 1 expression inhibited P53, KAI1/CD82, matrix metalloproteinase-9, and β-catenin but upregulated E-cadherin protein. MiR-217 overexpression induced reverse changes.

Conclusion: Hsa-miR-217 and its target sirtuin 1 acted as metastasis suppressor and promoter gene in non-small cell lung cancer, respectively. The hsa-miR-217/sirtuin 1/P53/KAI1 metastasis regulatory pathway showed novel and crucial roles in brain metastasis from non-small cell lung cancer. This axis might be a potential target for the treatment of brain metastasis of lung cancer.

Keywords: Brain metastasis; hsa-miRNA-217; lung cancer; PC-14/B cells; sirtuin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / etiology
  • Brain Neoplasms / physiopathology
  • Brain Neoplasms / prevention & control
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Cell Culture Techniques / methods
  • Cell Proliferation / drug effects
  • Humans
  • Kangai-1 Protein / drug effects*
  • MicroRNAs / pharmacology*
  • MicroRNAs / therapeutic use
  • Signal Transduction / drug effects
  • Sirtuin 1 / drug effects*
  • Tumor Suppressor Protein p53 / drug effects*


  • CD82 protein, human
  • Kangai-1 Protein
  • MIRN217 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • SIRT1 protein, human
  • Sirtuin 1