MiR-320a-3p/ELF3 axis regulates cell metastasis and invasion in non-small cell lung cancer via PI3K/Akt pathway

Gene. 2018 Sep 5:670:31-37. doi: 10.1016/j.gene.2018.05.100. Epub 2018 May 24.

Abstract

MicroRNAs (miRNAs) play important roles in tumorigenesis and tumor progression. In this study, we investigated the role of miR-320a-3p in non-small cell lung cancer (NSCLC). Expressions of miR-320a-3p were firstly determined in 80 NSCLC patients' cancer tissues and adjacent normal lung tissues by qRT-PCR. Then MTT assay, cell migration and invasion assays were performed in vitro. Potential binding sites on target gene of miR-320a-3p were predicted and luciferase reporter assay was used to identify the potential binding sites. Tumorigenesis assay were performed in nude mice by injecting A549 cells which stably express miR-320a-3p. Results indicated that high expression of miR-320a-3p suppresses cell proliferation, migration and invasion through the inactivation of PI3K/Akt signaling pathway in NSCLC cells. Smaller tumor size and lighter weight were also found in nude mice which had miR-320a-3p higher expressed. Furthermore, data from luciferase reporter assay proved the direct binding of miR-320a-3p on the 3'UTR region of ELF3 mRNA, this could further decrease ELF3 expression transcriptionally. We provided evidence that miR-320a-3p might work as a tumor suppressor in NSCLC both in vivo and in vitro.

Keywords: ELF3; NSCLC; PI3K/Akt; miR-320a-3p.

MeSH terms

  • A549 Cells
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-ets / genetics*
  • Signal Transduction*
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • ELF3 protein, human
  • MIRN320 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-ets
  • Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt