MiR-33b-5p sensitizes gastric cancer cells to chemotherapy drugs via inhibiting HMGA2 expression

J Drug Target. 2017 Aug;25(7):653-660. doi: 10.1080/1061186X.2017.1323220. Epub 2017 May 11.

Abstract

MicroRNAs (miRNAs) are internal, non-coding, and ∼22 nt small RNAs that display cell- and tissue-specific expression. They play important regulatory roles in cell proliferation and chemo-sensitivity. This study focused on tumor-suppressive miR-33b-5p expression as well as its role in gastric cancer. MiR-33b-5p was found low expression in gastric cancer cell lines. Functionally, western blots and the luciferase reporter assay were used to confirm that HMGA2 was the potential target of miR-33b-5p. Next, we used CCK-8 kits to analyze the effect of miR-33b-5p combined chemotherapy drugs on cell inhibition rate, and flow cytometry to analyze cells apoptosis. Colony formation ability was determined by plating at 500 cells per well into six-well plates and culturing for 15 d. The results showed that upregulation of miR-33b-5p decreased expression of HMGA2 and inhibited gastric cancer cell growth as well as sensitized gastric cancer cells to chemotherapy drugs. MiR-33b-5p overexpression hindered luciferase activity of HMGA2,3'-untranslated region-based reporter construct in 293 T cells. These data demonstrate that miR-33b-5p may be a potential therapeutic target for gastric cancer and function as tumor-suppressive miRNA through targeting HMGA2 in gastric cancer.

Keywords: HMGA2; MiR-33b-5p; chemo-sensitivity; gastric cancer.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Blotting, Western
  • Cell Line, Tumor
  • Flow Cytometry
  • HMGA2 Protein / genetics*
  • HMGA2 Protein / metabolism
  • Humans
  • MicroRNAs / physiology*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • HMGA2 Protein
  • MIRN33a microRNA, human
  • MicroRNAs