miR-338-3p suppresses gastric cancer progression through a PTEN-AKT axis by targeting P-REX2a

Bo Guo1, Liying Liu, Jiayi Yao

  • 1Xi'an Jiaotong University College of Medicine, Yanta Western Road 76, Xi'an 710061, China. hchen@mail.xjtu.edu.cn.

Abstract

Insights

MicroRNA-338-3p (miR-338-3p) is downregulated in gastric cancer and acts as a tumor suppressor. It inhibits cancer cell growth by targeting P-Rex2a and activating PTEN-AKT signaling, offering a new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant microRNA (miRNA) expression is observed in various cancers.
  • While miR-338-3p is linked to liver cancer, its function in gastric cancer remains unclear.

Purpose of the Study:

  • To investigate the role and mechanism of miR-338-3p in gastric cancer progression.

Main Methods:

  • Quantitative real-time PCR to assess miR-338-3p levels in gastric cancer tissues and cell lines.
  • Cell proliferation, clonogenicity, cell cycle, and apoptosis assays.
  • Western blotting to analyze protein expression and signaling pathways (PTEN, AKT).
  • In vivo tumor xenograft assays in nude mice.

Main Results:

  • miR-338-3p was significantly downregulated in gastric cancer tissues and cell lines.
  • Forced miR-338-3p expression suppressed gastric cancer cell proliferation, clonogenicity, induced G1-S arrest, and promoted apoptosis.
  • P-Rex2a was identified as a direct target of miR-338-3p; silencing P-Rex2a mimicked miR-338-3p effects.
  • miR-338-3p and P-Rex2a silencing activated PTEN, reducing AKT phosphorylation.
  • miR-338-3p inhibited tumor growth in vivo.

Conclusions:

  • miR-338-3p functions as a tumor suppressor in gastric cancer.
  • It inhibits gastric cancer progression by targeting P-Rex2a and modulating the PTEN-AKT signaling pathway.
  • miR-338-3p represents a potential therapeutic target for gastric cancer treatment.

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