Hsa-miR-100-5p promotes the development and progression of gastric cancer through targeted atypical chemokine receptor 3.

Abstract

Objectives: Gastric cancer (GC) ranks as the fourth most prevalent malignancy globally and is a leading cause of cancer-related mortality. This study aims to comprehensively investigate the pathogenesis of gastric cancer and propose innovative strategies for early diagnosis.

Methods: Leveraging data from The Cancer Genome Atlas (TCGA), we identified that hsa-miR-100-5p exhibits significantly reduced expression in gastric cancer tissues compared to normal tissues. Subsequently, the low expression levels and clinical significance of hsa-miR-100-5p were further validated through quantitative analysis in a cohort of 58 GC patients.

Results: Treatment with an hsa-miR-100-5p mimic markedly inhibited the proliferation of BGC823 cells, whereas the introduction of an hsa-miR-100-5p inhibitor promoted cell proliferation. A dual-luciferase reporter assay confirmed that atypical chemokine receptor 3 (ACKR3) is a direct target gene of hsa-miR-100-5p. Furthermore, our findings revealed a significant negative correlation between ACKR3 expression and hsa-miR-100-5p levels. Immunological correlation analysis suggested that ACKR3 may play a critical role in modulating the tumor microenvironment within cancer-associated fibroblasts.

Conclusion: Collectively, these results indicate that hsa-miR-100-5p may regulate ACKR3 to enhance the migration and proliferation of GC cells, thereby contributing to the onset and progression of gastric cancer.