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Original Article: MicroRNA Dysregulation in the Gastric Carcinogenesis Cascade: Can We Anticipate Its Role in

Inês Pita1, Diogo Libânio1,2, Francisca Dias3,4

  • 1Gastroenterology Department, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.

Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology
|July 18, 2021
PubMed
Abstract

Insights

MicroRNA (miRNA) dysregulation in gastric carcinogenesis involves specific molecules. miR-146a and miR-370 may act as tumor suppressors, while miR-21, miR-181b, and miR-490 show oncogenic potential in early gastric neoplasia.

Area of Science:

  • Gastroenterology and Molecular Oncology
  • Biomarker Discovery

Background:

  • Gastric carcinogenesis involves a progression from normal mucosa through atrophic gastritis and dysplasia to adenocarcinoma.
  • MicroRNAs (miRNAs) are key regulators of gene expression and are implicated in various cancers, including gastric cancer, though their precise roles are still under investigation.

Purpose of the Study:

  • To investigate and characterize the expression patterns of specific microRNAs (miRNAs) in both plasma and tissue samples across different stages of gastric carcinogenesis.
  • To determine the potential role of these miRNAs as biomarkers in the progression of gastric cancer.

Main Methods:

  • A single-center, cross-sectional study involving 64 patients, categorized into normal mucosa (19 controls), extensive atrophic/metaplastic gastritis (15), and early gastric neoplasia (EGN) (30).
  • Quantitative real-time PCR was used to measure the expression levels of seven selected miRNAs (miR-21, miR-146a, miR-181b, miR-370, miR-375, and miR-490) in peripheral blood and endoscopic biopsy specimens.

Main Results:

  • Significant upregulation of miR-181b, miR-490, and miR-21 was observed in the EGN mucosa compared to controls (2-14 times higher).
  • Significant underexpression of miR-146a and miR-370 was found in both atrophic/metaplastic gastritis and EGN tissues compared to controls (66-89% reduction).
  • No significant differences in miRNA expression were detected between neoplastic lesions and non-neoplastic mucosa, and plasma miRNA levels showed no significant dysregulation.

Conclusions:

  • Five miRNAs (miR-21, miR-146a, miR-181b, miR-370, miR-490) exhibit significant dysregulation during gastric carcinogenesis.
  • miR-146a and miR-370 may function as tumor suppressors, whereas miR-21, miR-181b, and miR-490 show potential as oncogenes in gastric cancer development.
  • The diffuse changes in miRNA expression within the gastric mucosa suggest a 'field defect' that could be crucial for patient surveillance strategies.
Keywords:
Gastric cancerGastric carcinogenesisGastric preneoplastic conditionsmicroRNAs

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