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sMicroRNA-28-5p acts as a metastasis suppressor in gastric cancer by targeting Nrf2

Cai-Feng Yue1, Lai-Sheng Li2, Lu Ai2

  • 1Department of Laboratory Medicine, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, 524045, PR China.

Experimental Cell Research
|March 19, 2021
PubMed

Insights

MicroRNA-28-5p acts as a tumor suppressor in gastric cancer by inhibiting Nrf2 expression, reducing cell migration and invasion. This finding suggests miR-28-5p as a potential biomarker and therapeutic target for gastric cancer.

Area of Science:

  • Molecular Oncology
  • Cancer Biology
  • Gene Regulation

Background:

  • Nuclear factor (erythroid-2)-related factor 2 (Nrf2) promotes cancer cell survival and is upregulated in gastric cancer (GC).
  • MicroRNA-28 (miR-28) regulates Nrf2 in breast cells, but its role in GC is uncharacterized.

Purpose of the Study:

  • To investigate the interaction between miR-28-5p and Nrf2 in gastric cancer.
  • To elucidate their roles in GC cell migration, invasion, and metastasis.

Main Methods:

  • Analysis of Nrf2 expression in GC tissues (n=42) via immunohistochemistry, RT-qPCR, and Western blot.
  • Bioinformatics analysis and dual luciferase reporter assay to confirm miR-28-5p targeting of Nrf2.
  • Gain- and loss-of-function studies to assess effects on GC cell behavior and epithelial-mesenchymal transition (EMT) markers.

Main Results:

  • Nrf2 was significantly upregulated in GC tissues, correlating with poor prognosis.
  • miR-28-5p directly targets and downregulates Nrf2 expression.
  • Overexpression of miR-28-5p or Nrf2 knockdown reduced GC cell migration, invasion, and N-cadherin expression while increasing E-cadherin.
  • miR-28-5p inhibited GC cell metastasis and tumorigenicity.

Conclusions:

  • miR-28-5p functions as a tumor suppressor in GC by inhibiting Nrf2.
  • miR-28-5p represses GC cell migration and invasion, potentially via regulating EMT.
  • miR-28-5p shows promise as a prognostic biomarker and therapeutic target for advanced GC.
Keywords:
Gastric cancerInvasionMetastasisMigrationNrf2microRNA-28-5p

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