Downregulation of miR‑7 and miR‑153 is involved in Helicobacter pylori CagA induced gastric carcinogenesis and progression

Int J Oncol. 2023 Jul;63(1):79. doi: 10.3892/ijo.2023.5527. Epub 2023 May 26.

Abstract

Helicobacter pylori (H. pylori) infection plays a pivotal role in the development of gastric cancer (GC). However, the association between aberrant microRNAs (miRNAs/miRs) expression and H. pylori‑induced GC remains poorly understood. The present study reported that repeated infection of H. pylori caused the oncogenicity of GES‑1 cells in BALB/c Nude mice. miRNA sequencing revealed that both miR‑7 and miR‑153 were significantly decreased in the cytotoxin‑associated gene A (CagA) positive GC tissues and this was further confirmed in a chronic infection model of GES‑1/HP cells. Further biological function experiments and in vivo experiments validated that miR‑7 and miR‑153 can promote apoptosis and autophagy, inhibit proliferation and inflammatory response in GES‑1/HP cells. All the associations between miR‑7/miR‑153 and their potential targets were revealed via bioinformatics prediction and dual‑luciferase reporter assay. Particularly, downregulation of both miR‑7 and miR‑153 obtained an improved sensitivity and specificity in diagnosing H. pylori (CagA+)‑induced GC. The present study identified that the combination of miR‑7 and miR‑153 may be regarded as novel therapeutic targets in H. pylori CagA (+)‑associated GC.

Keywords: Helicobacter pylori; cytotoxin‑associated gene A; gastric cancer; miR‑153; miR‑7.

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Bacterial Proteins / genetics
  • Carcinogenesis / genetics
  • Down-Regulation
  • Helicobacter Infections* / complications
  • Helicobacter Infections* / genetics
  • Helicobacter pylori* / genetics
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Stomach Neoplasms* / metabolism

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • MicroRNAs

Grants and funding

The present study was funded by the National Natural Science Foundation of China (grant no. 82102398), Shandong Provincial Natural Science Foundation (grant nos. ZR2020QC073, ZR2021MH409 and ZR2020MH296), Shandong Province Medical and Health Science and Technology Development Plan (grant nos. 2018WS106 and 202211000314) and the Incubation Project of Weihai Municipal Hospital (grant nos. FH-2021-XZ02 and FH-2021-JY16).