miR-885-5p Inhibits Invasion and Metastasis in Gastric Cancer by Targeting Malic Enzyme 1

DNA Cell Biol. 2021 May;40(5):694-705. doi: 10.1089/dna.2020.6478. Epub 2021 Mar 22.

Abstract

Several studies have reported that miR-885-5p was dysregulated in a variety of cancers. However, there are few studies on the biological function of miR-885-5p in gastric cancer (GC). In this study, we investigated the biological function and underlying mechanism of miR-885-5p in GC. Quantitative real-time PCR was used to examine the expression of miR-885-5p in GC. Bioinformatics analysis was used to predict the target of miR-885-5p and confirmed using the luciferase reporter assay. Wound-healing and Transwell assay were conducted to evaluate the biological function of miR-885-5p and malic enzyme 1 (ME1). Western blotting was used to assess molecular changes. Hepatic and lung metastasis models were constructed and used to verify the role of miR-885-5p. We found that the expression of miR-885-5p was significantly downregulated in GC. Overexpression of miR-885-5p inhibited invasion and metastasis of GC in vivo and in vitro, while inhibition of miR-885-5p has the opposite result in vitro. ME1 is a direct target of miR-885-5p, overexpressed in GC, associated with poor prognosis. Overexpression of miR-885-5p negatively regulates ME1 and causes changes in downstream molecules Vimentin and Fibronectin. Our research found that miR-885-5p plays a tumor suppressor gene and could potentially serve as a biomarker and therapeutic target in GC.

Keywords: ME1; gastric cancer; invasion; metastasis; miR-885-5p.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Down-Regulation / genetics
  • Female
  • Fibronectins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis / pathology
  • Malate Dehydrogenase / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Up-Regulation / genetics
  • Vimentin / metabolism

Substances

  • Fibronectins
  • MIRN885 microRNA, human
  • MicroRNAs
  • Vimentin
  • Malate Dehydrogenase
  • malate dehydrogenase (decarboxylating)