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Published on: October 15, 2018
Unveiling the oncogenic significance of thymidylate synthase in human cancers
Yibo Geng1, Luyang Xie2, Yang Wang1
1Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University Beijing, China.
Objective:
Thymidylate synthase (TYMS) constitutes a pivotal and potent target in the context of chemoresistance. However, the oncogenic role of TYMS has received insufficient attention.
Methods:
Leveraging data from the Cancer Genome Atlas (TCGA) and various public databases, we conducted an extensive investigation into the oncogenic role of TYMS across 33 cancer types. Subsequently, TYMS was inhibited using small interfering RNA (siRNA) in four different cell lines, and cell proliferation and migration were assessed using CellTiter-Glo and Transwell assays.
Results:
TYMS exhibited pronounced expression across a spectrum of cancers and demonstrated associations with clinical outcome in diverse cancer patient cohorts. Furthermore, genetic alterations were identified as potential influencers of overall survival in specific tumor types. Notably, the expression of thymidylate synthase correlated with tumor-infiltrating CD4+ cells in select cancers. Additionally, the functional mechanism of TYMS encompassed nucleotidase activity, chromosome segregation, and DNA replication progress. In vitro experiments further substantiated these findings, demonstrating that the suppression of TYMS impeded the cell growth and invasive capabilities of HeLa, A549, 786-O, and U87_MG cells.
Conclusions:
This study furnishes a comprehensive understanding of the oncogenic role played by TYMS in human tumors.
Insights
Thymidylate synthase (TYMS) is a key target in cancer treatment. This study reveals its significant oncogenic role across many cancers, impacting cell growth and migration.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Thymidylate synthase (TYMS) is a critical target for chemotherapy, particularly in overcoming chemoresistance.
- The broader oncogenic functions of TYMS beyond its role in chemoresistance remain underexplored.
Purpose of the Study:
- To comprehensively investigate the oncogenic role of TYMS across various human cancers.
- To elucidate the functional mechanisms and clinical implications of TYMS expression and alterations.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and public databases for multi-cancer analysis.
- Performed in vitro experiments involving TYMS inhibition via small interfering RNA (siRNA) in four cancer cell lines.
- Assessed cell proliferation and migration using CellTiter-Glo and Transwell assays.
Main Results:
- TYMS demonstrated significant expression across numerous cancer types, correlating with clinical outcomes.
- Genetic alterations in TYMS influenced overall survival in specific cancer types.
- TYMS inhibition in vitro reduced cancer cell proliferation and migration, highlighting its functional role in cell growth and invasion.
- Identified nucleotidase activity, chromosome segregation, and DNA replication as functional mechanisms of TYMS.
Conclusions:
- This research provides a thorough understanding of TYMS's oncogenic functions in human tumors.
- Highlights TYMS as a potential therapeutic target for enhancing cancer treatment strategies.
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