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Published on: October 22, 2021
Proteome and transcriptome analysis of cell death induced by 5-fluoro-2'-deoxyuridine
Akira Sato1, Eriko Miyazaki, Akito Satake
1Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.
Abstract:
5-fluoro-2'-deoxyuridine (FUdR) inhibits thymidylate synthase. We have been investigated the molecular mechanisms of cell death in mouse mammary tumor FM3A cells, F28-7 strain and its mutant F28-7-A strain, after treated with FUdR. Previously, we have been reported that F28-7 strain induced DNA cleavage into chromosomal sized fragments and subsequently develop necrosis, but F28-7-A strain induced DNA cleavage into oligonucleosomal sized fragments and subsequently develop apoptosis after treated with FUdR. To understand the molecular mechanisms of regulate of two differential cell death necrosis and apoptosis, we identify cell death regulator by using proteome and transcriptome analysis. When compared with the proteome of F28-7 and F28-7-A strain after treated with FUdR, it was found that 5 proteins were up-regulated and 11 proteins were down-regulated in F28-7-A strain. Furthermore, transcriptome analysis shows that 94 genes were up-regulated and 164 genes were downregulated in F28-7-A strain. Identified proteins and genes were involved in various cellular processes such as cell cycle regulation, apoptosis, proliferation, and differentiation. Our results suggested that numerous features indicated the coordinated regulation of molecular networks from various aspects of necrosis or apoptosis at the proteome and transcriptome levels.
Insights
5-fluoro-2'-deoxyuridine (FUdR) triggers distinct cell death pathways in mouse mammary tumor cells. Proteome and transcriptome analyses reveal molecular regulators governing necrosis versus apoptosis, offering insights into differential cell death mechanisms.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- 5-fluoro-2 -deoxyuridine (FUdR) is a thymidylate synthase inhibitor.
- Mouse mammary tumor FM3A cells exhibit differential responses to FUdR, leading to necrosis or apoptosis.
- Understanding the molecular mechanisms of these distinct cell death pathways is crucial.
Purpose of the Study:
- To investigate the molecular mechanisms underlying differential cell death (necrosis vs. apoptosis) induced by FUdR.
- To identify key protein and gene regulators involved in these distinct cellular fates.
- To elucidate the coordinated regulation of molecular networks at proteome and transcriptome levels.
Main Methods:
- Proteome analysis comparing FUdR-treated F28-7 and F28-7-A cell strains.
- Transcriptome analysis comparing FUdR-treated F28-7 and F28-7-A cell strains.
- Identification and functional annotation of differentially expressed proteins and genes.
Main Results:
- FUdR treatment induced necrosis in F28-7 cells (chromosomal DNA fragmentation) and apoptosis in F28-7-A cells (oligonucleosomal DNA fragmentation).
- Proteome analysis revealed 5 up-regulated and 11 down-regulated proteins in F28-7-A cells compared to F28-7 cells.
- Transcriptome analysis identified 94 up-regulated and 164 down-regulated genes in F28-7-A cells compared to F28-7 cells.
- Identified proteins and genes are implicated in cell cycle regulation, apoptosis, proliferation, and differentiation.
Conclusions:
- Differential cell death pathways (necrosis and apoptosis) are regulated by distinct molecular networks.
- Proteome and transcriptome analyses provide a comprehensive view of regulators involved in FUdR-induced differential cell death.
- These findings highlight the coordinated regulation of molecular networks governing cellular fate decisions.
