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Downregulation of CENPF Remodels Prostate Cancer Cells and Alters Cellular Metabolism
Muhammad Shahid1, Minhyung Kim1, Min Young Lee2
1Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Abstract:
Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the CENPF network, additional associations with lipid regulation are found. Further untargeted metabolomics analysis using gas chromatography-time-of-flight-mass spectrometry reveals that silencing of CENPF alters the global metabolic profiles of PC cells and inhibits cell proliferation, which suggests that CENPF may be a critical regulator of PC metabolism. These findings provide useful scientific insights that can be applied in future studies investigating potential targets for PC treatment.
Insights
Centromere protein F (CENPF) significantly impacts prostate cancer (PC) metabolism and progression. Silencing CENPF alters cell metabolism and inhibits proliferation, revealing its role in aggressive PC.
Area of Science:
- Oncology
- Molecular Biology
- Metabolomics
Background:
- Metabolic reprogramming is a hallmark of aggressive prostate cancer (PC).
- The specific mechanisms driving PC metabolic dysregulation remain largely unexplored.
- Centromere protein F (CENPF) was previously linked to PC MRI visibility.
Purpose of the Study:
- To investigate the role of CENPF in metabolic alterations within human PC3 prostate cancer cells.
- To determine if CENPF influences PC aggressiveness and metastatic potential.
- To elucidate CENPF's involvement in regulating cellular metabolism.
Main Methods:
- Bioinformatic analyses to identify genes associated with aggressive PC and metastasis.
- Network reconstruction to explore CENPF interactions.
- Untargeted metabolomics using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS).
- Experimental silencing of CENPF in PC3 cells.
Main Results:
- CENPF expression is strongly correlated with aggressive PC and metastasis.
- The CENPF network is associated with lipid regulation pathways.
- Silencing CENPF significantly altered global metabolic profiles in PC cells.
- CENPF inhibition led to reduced PC cell proliferation.
Conclusions:
- CENPF plays a critical role in regulating prostate cancer cell metabolism.
- CENPF is implicated in PC progression and aggressiveness.
- Targeting CENPF may offer a novel therapeutic strategy for prostate cancer.
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