Oleanolic acid regulates the Treg/Th17 imbalance in gastric cancer by targeting IL-6 with miR-98-5p

Cytokine. 2021 Dec:148:155656. doi: 10.1016/j.cyto.2021.155656. Epub 2021 Aug 11.

Abstract

Background: Gastric cancer (GC) was a type of malignant tumor with a very high fatality rate. Oleanolic acid (OA) was a class of pentacyclic triterpenes which was proved to have anti-cancer activity. While the specific molecular mechanism of OA's role in inhibiting GC was not fully understood. This study aimed to explore how OA played an anti-cancer role in GC.

Methods: Expression of miR-98-5p was examined using qPCR, and expression levels of Treg/Th17-related factors were evaluated using qPCR and western blot. Flow cytometry was conducted to assess the proportion of Treg cells and Th17 cells. Besides, dual luciferase reporter assay was performed to verify that IL-6 was a target of miR-98-5p.

Results: Downregulation of miR-98-5p and upregulation of Treg/Th17-related factors were observed in GC tissues. What's more, the Treg/Th17 imbalance was found in PBMCs of GC patients. Overexpression of miR-98-5p promoted balance of Treg/Th17 cells via directly targeting IL-6 to downregulate expression of IL-6. Finally, OA could promote balance of Treg/Th17 cells by upregulating expression of miR-98-5p.

Discussion: All our results proved that OA could promote balance of Treg/Th17 cells in GC by targeting IL-6 with miR-98-5p, indicating a potential drug for treatment of GC.

Keywords: Gastric cancer; IL-6; MiR-98-5p; Oleanolic acid; Treg/Th17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-6 / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oleanolic Acid / pharmacology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*

Substances

  • Interleukin-6
  • MIRN98 microRNA, human
  • MicroRNAs
  • Oleanolic Acid