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RUNX1, FUS, and ELAVL1-induced circPTPN22 promote gastric cancer cell proliferation, migration, and invasion through miR-6788-5p/PAK1 axis-mediated autophagy

  • 0Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Xisi Road, NO.20, Nantong, 226001, Jiangsu, China.
Cellular & Molecular Biology Letters +

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July 3, 2024

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July 3, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Circular RNA PTPN22 (circPTPN22) inhibits autophagy and promotes gastric cancer (GC) progression by regulating the miR-6788-5p/PAK1 pathway. This creates a positive feedback loop, accelerating GC development.

Area Of Science

  • Molecular Biology
  • Oncology
  • Cell Biology

Background

  • Circular RNAs (circRNAs) are implicated in various diseases, including cancer.
  • The specific roles of circRNAs in gastric cancer (GC) autophagy remain unclear.

Purpose Of The Study

  • To elucidate the function and mechanism of circPTPN22 in regulating autophagy during gastric cancer progression.
  • To investigate the molecular pathways involved in circPTPN22-mediated GC development.

Main Methods

  • Investigated autophagy using transmission electron microscopy and mRFP-GFP-LC3 assays.
  • Assessed GC progression markers (proliferation, migration, invasion) via CCK-8, colony formation, EdU, and Transwell assays.
  • Validated molecular interactions using dual-luciferase reporter assays, Western blots, and in vivo xenograft models.

Main Results

  • circPTPN22 upregulation inhibits autophagy and promotes GC cell proliferation, migration, and invasion.
  • circPTPN22 targets miR-6788-5p, regulating PAK1, Akt, and Erk phosphorylation, thereby affecting autophagy.
  • RUNX1 negatively regulates circPTPN22, while FUS and ELAVL1 positively regulate it, with autophagy inhibition increasing FUS and circPTPN22.

Conclusions

  • circPTPN22, regulated by RUNX1, FUS, and ELAVL1, promotes GC via the miR-6788-5p/PAK1 axis, impacting Akt/Erk phosphorylation and autophagy.
  • A positive feedback loop exists where autophagy inhibition increases FUS, further upregulating circPTPN22 and accelerating GC progression.

Keywords:

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