Selenoprotein W modulates control of cell cycle entry

Area of Science:

• Cell Biology
• Molecular Biology
• Nutritional Science

Background:

• Selenium (Se) is an essential trace element with known antioxidant and anticancer properties.
• Understanding the specific molecular targets of selenium in human cells is crucial for elucidating its physiological roles.
• Physiologically relevant doses and forms of selenium are important for accurate target identification.

Purpose of the Study:

• To identify the molecular targets of selenium in cultured human breast and prostate epithelial cells.
• To investigate the role of specific selenoproteins, such as Selenoprotein W (SEPW1), in cellular processes.
• To determine the impact of selenium supplementation on cell cycle regulation.

Main Methods:

• Gene expression profiling using DNA microarrays in MCF-10A breast cells and prostate epithelial cells.
• Supplementation with selenium in the form of sodium selenite or high-selenium serum.
• Functional studies using small interfering RNA (siRNA) to knockdown SEPW1 expression.
• Analysis of cell cycle progression and gene expression changes.

Main Results:

• Sodium selenite significantly altered the expression of 560 genes in breast cells, with 60 genes related to the cell cycle.
• Selenoprotein W (SEPW1) mRNA was the only selenoprotein mRNA upregulated by both sodium selenite and high-selenium serum.
• SEPW1 knockdown inhibited cell cycle progression at the G1/S transition and altered the expression of cell cycle regulatory genes (BCL2, RBBP8, KPNA2).

Conclusions:

• SEPW1 is a physiological target of selenium in breast and prostate epithelial cells.
• Selenium influences cell cycle progression, specifically at the G1/S transition, potentially through SEPW1.
• These findings contribute to understanding the molecular mechanisms underlying selenium's effects on epithelial cell function.