MicroRNA-197 induces epithelial-mesenchymal transition and invasion through the downregulation of HIPK2 in lung adenocarcinoma

J Genet. 2018 Mar;47(1):47-53.

Abstract

The major cause of cancer-related deaths in patients with lung adenocarcinoma (LAD) is due to distant metastasis. Many reports have indicated that miRNA plays a key role in tumour metastasis. The expression of miR-197 is correlated with LADprogression, however, the mechanism of miR-197 is still unknown in the processing of LAD. A Boyden chamber migration/invasion assay was used for the metastatic function study in vitro. Real-time PCR andWestern blot assays were employed to analyse the EMT hallmark changes in both the mRNA and protein levels. 3'-UTR reporter luciferase assay was used to show that HIPK2 is a directtarget of miR-197. miR-197 enhances LAD cell migration and invasion miR-197. The downregulation of miR-197 suppresses the EMT and migration ability. HIPK2 is a direct functional target of miR-197 in LAD metastasis. In summary, miR-197 controls EMT and metastasis by directly silencing HIPK2. The findings suggest that interfering with the miR-197-dependent regulation of HIPK2 could be a useful approach for the treatment of patients with late stage metastatic LAD.

MeSH terms

  • A549 Cells
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference

Substances

  • Carrier Proteins
  • MIRN197 microRNA, human
  • MicroRNAs
  • HIPK2 protein, human
  • Protein Serine-Threonine Kinases