MiR-376a suppresses the proliferation and invasion of non-small-cell lung cancer by targeting c-Myc

Cell Biol Int. 2018 Jan;42(1):25-33. doi: 10.1002/cbin.10828. Epub 2017 Sep 11.

Abstract

It has been reported that miR-376a is involved in the formation and progression of several types of cancer. However, the expression and function of miR-376a is still unknown in non-small cell lung carcinomas (NSCLC). In this study, the expression of miR-376a in NSCLC tissues and cell lines were examined by real-time PCR, the effects of miR-376a on cell proliferation, apoptosis and invasion were evaluated in vitro. Luciferase reporter assay was performed to identify the targets of miR-376a. The results showed that miR-376a was significantly downregulated in NSCLC tissues and cell lines. Restoration of miR-376a in NSCLC cell line A549 significantly inhibited cell proliferation, increased cell apoptosis and suppressed cell invasion, compared with control-transfected A549 cells. Luciferase reporter assay showed that c-Myc, an oncogene that regulating cell survival, angiogenesis and metastasis, was a direct target of miR-376a. Over-expression of miR-376a decreased the mRNA and protein levels of c-Myc in A549 cells. In addition, upregulation of c-Myc inhibited miR-376a-induced inhibition of cell proliferation and invasion in A549 cells. Therefore, our results indicate a tumor suppressor role of miR-376a in NSCLC by targeting c-Myc. miR-376a may be a promising therapeutic target for NSCLC.

Keywords: NSCLC; c-Myc; miR-376a; tumor suppressor.

MeSH terms

  • A549 Cells
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation
  • Genes, myc*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Transcriptome
  • Transfection

Substances

  • MIRN376C microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc