MicroRNA-585 acts as a tumor suppressor in non-small-cell lung cancer by targeting hSMG-1

Clin Transl Oncol. 2017 May;19(5):546-552. doi: 10.1007/s12094-016-1562-5. Epub 2016 Oct 14.

Abstract

Purpose: To investigate the role of miR-585 in the development and progression of non-small-cell lung cancer (NSCLC).

Methods: The expression levels of miR-585 in NSCLC cell lines and clinical samples were measured by quantitative PCR. NSCLC cells, A549 and H1299, were stably transfected with lentiviral vectors of miR-585 mimics or negative control. The effects of miR-585 on cell proliferation were detected both in vitro and in vivo. Cell migration and invasion were evaluated using wound healing assay and Transwell assay. Furthermore, luciferase reporter assay was used to identify the direct regulation of hSMG-1 by miR-585.

Results: Our results showed that miR-585 was downregulated in NSCLC cell lines and tumor tissues. Ectopic expression of miR-585 inhibited the ability of cell proliferation, migration, and invasion in vitro. In addition, miR-585 also decreased the growth rate of xenografted tumor in nude mice. Mechanically, miR-585 directly targeted the 3'-untranslated region (UTR) of hSMG-1 gene, which likely resulted in a dysfunction of mRNA surveillance and nonsense-mediated mRNA decay.

Conclusion: Taken together, miR-585 probably has an inhibitory effect on tumor growth and is a prognostic biomarker of NSCLC.

Keywords: Invasion; Non-small-cell lung cancer; Proliferation; hSMG-1; miR-585.

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Tumor Suppressor
  • Heterografts
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Metalloendopeptidases / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Polymerase Chain Reaction

Substances

  • MicroRNAs
  • Metalloendopeptidases
  • O-sialoglycoprotein endopeptidase