PCAT-1 contributes to cisplatin resistance in gastric cancer through miR-128/ZEB1 axis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Dysregulation of long non-coding RNAs (lncRNAs) is linked to cancer chemoresistance.
• The specific role of lncRNA PCAT-1 in gastric cancer (GC) cisplatin resistance is not fully understood.

Purpose of the Study:

• To investigate the functional role of lncRNA PCAT-1 in cisplatin resistance in GC.
• To elucidate the molecular mechanism underlying PCAT-1's role in GC chemoresistance.

Main Methods:

• Quantitative real-time PCR to measure PCAT-1 expression in GC tissues and cells.
• Cell viability assays and in vivo tumor xenografts to assess DDP sensitivity after PCAT-1 knockdown.
• Luciferase reporter assays and RNA immunoprecipitation to confirm the interaction between PCAT-1, miR-128, and ZEB1.

Main Results:

• PCAT-1 was significantly upregulated in cisplatin-resistant GC tissues and cells, correlating with poor prognosis.
• Knockdown of PCAT-1 increased GC cells' sensitivity to DDP both in vitro and in vivo.
• PCAT-1 acts as a molecular sponge for miR-128, and ZEB1 is a target of miR-128, forming the PCAT-1/miR-128/ZEB1 axis that mediates DDP resistance.

Conclusions:

• PCAT-1 confers cisplatin resistance in GC by regulating the miR-128/ZEB1 axis.
• PCAT-1 represents a potential therapeutic target for overcoming chemoresistance in gastric cancer.