MicroRNA-1246 inhibits cell invasion and epithelial mesenchymal transition process by targeting CXCR4 in lung cancer cells

Cancer Biomark. 2018 Feb 6;21(2):251-260. doi: 10.3233/CBM-170317.

Abstract

Background: Recent studies have indicated that microRNAs (miRNAs) are closely related to lung cancer. However, the effects of miR-1246 on lung cancer are still elusive. In this study, we aimed to explore the molecular mechanisms of miR-1246 in lung cancer.

Materials and methods: Using RT-qPCR assay, we analyzed the expression of miR-1246 in lung cancer cell lines and lung epithelial cell line. Using Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell, RT-qPCR and western blot assays, we investigated cell viability, apoptosis, invasion and epithelial mesenchymal transition (EMT) process. Using luciferase reporter assay, we confirmed a target of miR-1246. Using western blot assay, we detected the protein mechanisms of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signal pathways.

Results: Our results showed that miR-1246 was down-regulated in lung cancer cell lines (A549, H1650 and H1299) compared to in lung epithelial cell line (16HBE14o). MiR-1246 overexpression remarkably inhibited cell invasion as well as up-regulated E-cadherin expression and down-regulated N-cadherin, Vimentin, ZEB1 and Snail expressions in A549 cells. Further studies have confirmed CXCR4 as a target gene of miR-1246, and CXCR4 silence significantly abolished the promotion effect of miR-1246 suppression on cell invasion and EMT process in A549 cells. Besides, miR-1246 blocked JAK/STAT and PI3K/AKT signal pathways by regulation of CXCR4.

Conclusions: These results demonstrated that miR-1246 inhibited cell invasion and EMT process by targeting CXCR4 and blocking JAK/STAT and PI3K/AKT signal pathways in lung cancer cells.

Keywords: CXCR4; cell invasion; epithelial mesenchymal transition; lung cancer; microRNA-1246.

Publication types

  • Retracted Publication

MeSH terms

  • A549 Cells
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Down-Regulation
  • Epithelial-Mesenchymal Transition
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / metabolism
  • Signal Transduction
  • Transfection

Substances

  • CXCR4 protein, human
  • MIRN1246 microRNA, human
  • MicroRNAs
  • Receptors, CXCR4