Inhibitory Effect of MiR-449b on Cancer Cell Growth and Invasion through LGR4 in Non-Small-Cell Lung Carcinoma

Curr Med Sci. 2018 Aug;38(4):582-589. doi: 10.1007/s11596-018-1917-y. Epub 2018 Aug 20.

Abstract

Non-small-cell lung carcinoma (NSCLC) is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b (miR-449b) functions as a tumor suppressor in many cancers. However, the role of miR-449b in NSCLC is still unknown. In the present study, miR-449b was significantly downregulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3'-UTR region of leucine rich repeat containing G protein-coupled receptor 4 (LGR4) mRNA had putative complementary sequences to miR-449b,which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.

Keywords: growth; invasion; leucine rich repeat containing G protein-coupled receptor 4; microRNA-449b; non-small-cell lung carcinoma.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • LGR4 protein, human
  • MIRN449 microRNA, human
  • MicroRNAs
  • Receptors, G-Protein-Coupled