FOXP1 and NDRG1 act differentially as downstream effectors of RAD9-mediated prostate cancer cell functions

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Metastatic progression is the primary cause of prostate cancer mortality.
• RAD9 is an oncogene that promotes prostate cancer metastasis, but its downstream targets are not fully understood.

Purpose of the Study:

• To identify genes transcriptionally regulated by RAD9 in prostate cancer.
• To elucidate the role of RAD9-regulated genes, specifically FOXP1 and NDRG1, in prostate cancer progression.

Main Methods:

• Microarray gene expression profiling to identify RAD9-regulated genes.
• Chromatin immunoprecipitation to confirm RAD9 binding to target gene loci.
• siRNA-mediated knockdown of RAD9, FOXP1, and NDRG1 in prostate cancer cells.
• Functional assays assessing cell proliferation, migration, anchorage-independent growth, anoikis resistance, and aerobic glycolysis.

Main Results:

• RAD9 knockdown altered the expression of 44 genes, all bound by RAD9.
• RAD9, FOXP1, and NDRG1 were found to be downregulated upon RAD9 reduction.
• Reduced expression of RAD9, FOXP1, or NDRG1 impaired prostate cancer cell proliferation, migration, anchorage-independent growth, anoikis resistance, and aerobic glycolysis.
• FOXP1 partially restored multiple cellular functions, while NDRG1 only partially restored aerobic glycolysis in RAD9-deficient cells.

Conclusions:

• RAD9 directly regulates the expression of FOXP1 and NDRG1 in prostate cancer.
• FOXP1 and NDRG1 act as distinct downstream effectors of RAD9, influencing various prostate cancer cell activities.
• These findings highlight RAD9, FOXP1, and NDRG1 as potential therapeutic targets for prostate cancer treatment.