MiR-155 inhibits proliferation and invasion by directly targeting PDCD4 in non-small cell lung cancer

Thorac Cancer. 2017 Nov;8(6):613-619. doi: 10.1111/1759-7714.12492. Epub 2017 Aug 26.

Abstract

Background: MicroRNAs are often abnormally expressed in human non-small cell lung cancer (NSCLC) and are thought to play a critical role in the emergence or maintenance of NSCLC by binding to its target messenger RNA. We assessed the effects of miR-155 on cell proliferation and invasion to elucidate the role played by miR-155/PDCD4 in NSCLC.

Methods: Quantitative reverse transcription-PCR, Western blotting, and cell counting kit-8, luciferase, and transwell invasion assays were conducted on a normal human bronchial epithelial cell line (BEAS-2B) and three NSCLC cell lines (SPC-A-1, A549, and H2170).

Results: We confirmed that miR-155 was upregulated, while PDCD4 messenger RNA and protein levels were downregulated in NSCLC cell lines. miR-155 negatively regulated PDCD4 at both transcriptional and post-transcriptional levels. Moreover, PDCD4 was forecast as an assumed target of miR-155 using bioinformatic methods and we demonstrated that PDCD4 was a direct target of miR-155 using luciferase reporter assays. Furthermore, PDCD4 overexpression could restrain NSCLC proliferation and invasion induced by miR-155.

Conclusion: Our results collectively demonstrate that miR-155 exerts an oncogenic role in NSCLC by directly targeting PDCD4.

Keywords: Invasion; NSCLC; PDCD4; miR-155; proliferation.

MeSH terms

  • 3' Untranslated Regions
  • A549 Cells
  • Animals
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • MIRN155 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA-Binding Proteins