Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.
Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom; School of Biomedical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, United Kingdom; The Medical School, Newcastle University, Newcastle-upon-Tyne, United Kingdom; catherine.meplan@ncl.ac.uk.
Catherine
C
Méplan
Institute of Food Research, Norwich Research Park, Norwich, United Kingdom;
Ian T
IT
Johnson
Institute of Food Research, Norwich Research Park, Norwich, United Kingdom;
Abigael C J
AC
Polley
Bioinformatics Support Unit, Newcastle University, Newcastle-upon-Tyne, United Kingdom;
Simon
S
Cockell
Wansbeck General Hospital, Ashingon, United Kingdom; and.
David M
DM
Bradburn
Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, United Kingdom;
Daniel M
DM
Commane
School of Biomedical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Wansbeck General Hospital, Ashingon, United Kingdom; and **Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
Ramesh P
RP
Arasaradnam
Institute of Food Research, Norwich Research Park, Norwich, United Kingdom;
Francis
F
Mulholland
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom;
Anze
A
Zupanic
Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, United Kingdom; **Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
John C
JC
Mathers
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, United Kingdom; The Medical School, Newcastle University, Newcastle-upon-Tyne, United Kingdom;
John
J
Hesketh
D000328:Adult; D003599:Cytoskeleton / Q000187:drug effects*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D040901:Proteomics; D012004:Rectal Neoplasms / Q000378:metabolism*; D012007:Rectum / Q000166:cytology*; D012643:Selenium / Q000494:pharmacology*; D059467:Transcriptome
D012643:Selenium
NFκB; colorectal; cytokeratin; nutrigenomics; selenoprotein