miR‑593 inhibits proliferation and invasion and promotes apoptosis in non‑small cell lung cancer cells by targeting SLUG‑associated signaling pathways

Mol Med Rep. 2019 Dec;20(6):5172-5182. doi: 10.3892/mmr.2019.10776. Epub 2019 Oct 29.

Abstract

Increasing evidence suggests that microRNAs (miRNAs or miRs) serve a critical role in tumor development. However, the role of miRNAs in non‑small cell lung cancer (NSCLC) progression remains largely unknown. The present study observed that miR‑593 was significantly impaired in patients with NSCLC and was a novel regulator of NSCLC progression. Patients whose tumors had high expression levels of miR‑593 had longer overall survival than patients whose tumors had low levels of miR‑593 expression (P=0.0219). miR‑593 expression levels were inversely correlated with zinc finger protein SNAI2 (SLUG) messenger RNA (mRNA) levels in 87 clinical tissue specimens of NSCLC (P<0.001). A luciferase assay demonstrated that miR‑593 interacted with the binding sites present in the SLUG 3'‑untranslated region and reduced the expression of SLUG. Introduction of a miR‑593 mimic suppressed cell proliferation by inactivating the SLUG/protein kinase B (Akt)/cyclin D1/CDK4 or CDK6 signaling pathway, while it induced apoptosis by activating the SLUG/Akt/Bcl‑2/BAX signaling pathway. Furthermore, introduction of a miR‑593 mimic recovered the expression of E‑cadherin at the protein and mRNA level, and inhibited cell migration and invasion. In conclusion, these results indicated that miR‑593 may act as a tumor suppressor in NSCLC to decelerate cancer aggressiveness by inhibiting SLUG expression.

MeSH terms

  • Adult
  • Apoptosis / genetics*
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Interference*
  • Signal Transduction
  • Snail Family Transcription Factors / genetics*
  • Snail Family Transcription Factors / metabolism
  • Young Adult

Substances

  • Biomarkers
  • MIRN593 microRNA, human
  • MicroRNAs
  • SNAI1 protein, human
  • Snail Family Transcription Factors