PARI functions as a new transcriptional target of FOXM1 involved in gastric cancer development

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• The DNA repair protein PARI is implicated in pancreatic cancer's cell cycle regulation and carcinogenesis.
• The precise role and regulatory mechanisms of PARI in other cancers, particularly gastric cancer, remain largely unexplored.

Purpose of the Study:

• To investigate the expression of PARI in gastric cancer (GC).
• To characterize the functional role of PARI in GC development.
• To elucidate the regulatory relationship between PARI and the oncogene FOXM1 in GC.

Main Methods:

• Immunohistochemical analysis of PARI expression in GC tissues and adjacent normal tissues.
• In vitro assays (e.g., cell proliferation, migration, invasion) and in vivo animal models (xenograft tumor growth, lung metastasis) to assess PARI function.
• Quantitative real-time PCR, western blot, luciferase reporter assays, and chromatin immunoprecipitation assays to investigate the FOXM1-PARI regulatory axis.

Main Results:

• PARI protein expression was significantly higher in GC tissues compared to normal gastric mucosa.
• Knockdown of PARI inhibited GC cell proliferation, migration, and invasion in vitro, and reduced tumor growth and metastasis in vivo.
• FOXM1 directly activated PARI transcription, and PARI expression positively correlated with FOXM1 levels in GC samples.
• PARI knockdown counteracted FOXM1's pro-migratory effects on GC cells.

Conclusions:

• PARI exhibits oncogenic properties in gastric cancer.
• PARI acts as a transcriptional target and effector of FOXM1, contributing to GC development.
• The FOXM1-PARI pathway represents a potential therapeutic target for gastric cancer.