miR-24-3p/KLF8 Signaling Axis Contributes to LUAD Metastasis by Regulating EMT

J Immunol Res. 2020 Apr 28:2020:4036047. doi: 10.1155/2020/4036047. eCollection 2020.

Abstract

Reprogramming of the tumor immune microenvironment is a salient feature during metastasis in LUAD. miR-24-3p and KLF8, which are key regulators of the tumor immune microenvironment, had been proved to show metastasis-promoting property in LUAD. However, whether miR-24-3p could regulate LUAD metastasis by targeting KLF8 remains unclear. This study explored the functions and mechanisms of miR-24-3p/KLF8 signaling in advanced LUAD. The expression level of miR-24-3p and KLF8 were tested in LUAD patients, and the corelation of miR-24-3p and KLF8 was evaluated. The interaction of miR-24-3p and KLF8 was demonstrated by luciferase reporter activity assay, in vitro migration and invasion studies, and in vivo metastatic studies. miR-24-3p level was downregulated in LUAD and negatively associated with KLF8 mRNA expression. miR-24-3p controls LUAD metastasis by directly targeting KLF8 and inducing Snail and E-cadherin expressions. Targeting the miR-24-3p/KLF8/EMT axis might be of great therapeutic value to advanced LUAD patients.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / secondary
  • Animals
  • Antigens, CD / metabolism
  • Cadherins / metabolism
  • Cell Proliferation
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Kruppel-Like Transcription Factors / genetics*
  • Lung / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Signal Transduction / genetics
  • Snail Family Transcription Factors / metabolism
  • Tumor Microenvironment / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • KLF8 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN24 microRNA, human
  • MicroRNAs
  • SNAI1 protein, human
  • Snail Family Transcription Factors