MicroRNA-19a regulates the proliferation, migration and invasion of human gastric cancer cells by targeting CUL5

Arch Biochem Biophys. 2019 Feb 15:662:93-100. doi: 10.1016/j.abb.2018.11.023. Epub 2018 Dec 3.

Abstract

Gastric cancer is one of the prevalent types of cancers and despite improvements in its treatment, the overall survival is still far from descent. The dearth of efficient biomarkers, chemotherapeutic agents and therapeutic targets form a major hurdle in the treatment of the gastric cancer. Accumulating evidences suggest that MicroRNAs (miRs) may prove important therapeutic targets/agents for the management of cancers including gastric cancer. Herein, we examined the expression of miR-19a by qRT-PCR in gastric cancer and attempted to explore its potential role. It was found that the expression of miR-19a is significantly (p < 0.05) enhanced in the gastric cancer tissues as well as the gastric cancer cell lines. Inhibition of miR-19a in gastric cancer cells suppressed the proliferation migration and invasion of the gastric cancer cells. Bioinformatic analysis revealed CUL5 to be the potential target of miR-19a. Contrary, to the expression of miR-19a, the expression of CUL5 was significantly (p < 0.05) downregulated in all the gastric cancer tissues and cell lines. However, inhibition of miR-19a in SNU-16 gastric cancer cells could cause upsurge of CUL5 expression. Overexpression of CUL-5 was found to exhibit similar effects on the proliferation, migration and invasion of the SNU-16 gastric cancer cells as that of miR-19a suppression. Additionally, overexpression of CUL5 could at least partially abolish the effects of miR-19a suppression on the proliferation, migration and invasion of SNU-16 gastric cancer cells. Finally, overexpression of miR-19a caused inhibition of the xenografted tumors in vivo indicating the potential of miR-19a as therapeutic target for gastric cancer.

Keywords: CUL-5; Gastric cancer; Invasion; Migration; Proliferation; microRNA.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Cullin Proteins / physiology*
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / therapy
  • Up-Regulation

Substances

  • CUL5 protein, human
  • Cullin Proteins
  • MIRN19 microRNA, human
  • MicroRNAs