MicroRNA-181a-5p Impedes IL-17-Induced Nonsmall Cell Lung Cancer Proliferation and Migration through Targeting VCAM-1

Cell Physiol Biochem. 2017;42(1):346-356. doi: 10.1159/000477389. Epub 2017 May 25.

Abstract

Aim: The contribution of the inflammatory mediator interleukin-17 (IL-17) in nonsmall cell lung cancer (NSCLC) malignancy has been reported in the literature. MicroRNA-181a-5p (miR-181a-5p) acts as a tumor suppressor which can regulate target gene at the posttranscriptional level. Our study aimed to investigate the interaction between IL-17 and miR-181a-5p in NSCLC.

Methods: 35 patients with NSCLC and 24 COPD controls were selected and examined in our study. In vitro, H226 and H460 cell lines were exposed to different doses (20, 40, 60, and 80 ng/mL) of IL-17 to examine the effect of IL-17 on miR-181a-5p and vascular cell adhesion molecule 1 (VCAM-1) expression. MiR-181 mimic and miR-181a-5p inhibitor were transfected to explore the regulation of VCAM-1 as well as tumor cell proliferation and migration.

Results: miR-181a-5p expression was downregulated, and IL-17 and VCAM-1 expression was upregulated in NSCLC tissues. Furthermore, IL-17 decreased miR-181a-5p expression but increased VCAM-1 expression in H226 and H460 cells. MiR-181 regulated VCAM-1 expression through binding to 3'-UTR sequence. MiR-181 attenuated tumor cell proliferation and migration. IL-17 modulated miR-181a-5p expression through activating NF-κB but not Stat3.

Conclusion: Taken together, our data show the regulation of VCAM-1 expression by miR-181a-5p under IL-17 exposure, predicting a potential way for counteracting cancer metastasis.

Keywords: Interleukin-17; Migration; Nonsmall cell lung cancer; Proliferation; Vascular cell adhesion molecule 1; microRNA-181.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Antagomirs / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation / drug effects
  • Female
  • HEK293 Cells
  • Humans
  • Interleukin-17 / metabolism*
  • Interleukin-17 / pharmacology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA Interference
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Up-Regulation / drug effects
  • Vascular Cell Adhesion Molecule-1 / chemistry
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Antagomirs
  • Interleukin-17
  • MIrn181 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • STAT3 Transcription Factor
  • Vascular Cell Adhesion Molecule-1