TDO2 knockdown inhibits colorectal cancer progression via TDO2-KYNU-AhR pathway
Long Zhao1, Bo Wang2, Changjiang Yang1
1Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, PR China; Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, PR China.
Background:
The aim of this study was to explore the expression levels and biological significance of TDO2 in colorectal cancer (CRC).
Methods:
First, we explored the potential oncogenic roles of TDO2 across 33 tumors based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Second, we evaluated TDO2 protein expression in 55 CRC tissue samples and 30 cDNA samples by immunohistochemistry and qPCR. Third, we investigated the effect of TDO2 on CRC cells by cell proliferation, wound healing, invasion, and colony formation assays. Finally, we determined the protein that is most closely associated with TDO2 via bioinformatics analysis, enriched the key pathways, and verified them.
Results:
The expression level of TDO2 was found to be associated with the tumor clinical stage in CRC. A high expression of TDO2 was associated with a poor outcome in CRC patients. Inhibition of TDO2 expression by RNAi in LoVo and HCT116 cell lines significantly reduced the proliferation, migration, and invasion abilities as well as colony formation abilities of cells. Further, knockdown of TDO2 expression induced inactivation of the TDO2-KYNU-AhR signaling pathway.
Conclusion:
The results suggest that TDO2 plays an important role in the progression of CRC. Accordingly, TDO2 is a potential therapeutic target in CRC.
Insights
Tryptophan 2,3-dioxygenase (TDO2) is highly expressed in colorectal cancer (CRC) and linked to poor patient outcomes. Inhibiting TDO2 reduces CRC cell growth and invasion, suggesting TDO2 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) remains a significant global health challenge.
- Understanding the molecular mechanisms driving CRC progression is crucial for developing effective therapies.
- Tryptophan 2,3-dioxygenase (TDO2) is an enzyme with known roles in immune regulation and cancer, but its specific involvement in CRC requires further elucidation.
Purpose of the Study:
- To investigate the expression levels and biological significance of TDO2 in colorectal cancer (CRC).
- To determine the potential oncogenic roles and therapeutic implications of TDO2 in CRC.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to analyze TDO2 expression across 33 tumor types.
- Assessed TDO2 protein and mRNA expression in CRC tissues and cell lines using immunohistochemistry and quantitative polymerase chain reaction (qPCR).
- Performed in vitro functional assays (proliferation, migration, invasion, colony formation) to evaluate the impact of TDO2 inhibition on CRC cells.
- Conducted bioinformatics analysis to identify TDO2-associated proteins and key signaling pathways, followed by experimental verification.
Main Results:
- TDO2 expression levels correlated with tumor clinical stage in CRC patients.
- High TDO2 expression was significantly associated with poorer overall survival in CRC.
- RNA interference-mediated inhibition of TDO2 in CRC cell lines (LoVo, HCT116) markedly suppressed cell proliferation, migration, invasion, and colony formation.
- Knockdown of TDO2 led to the inactivation of the TDO2-KYNU-AhR signaling pathway.
Conclusions:
- TDO2 plays a critical role in the progression of colorectal cancer.
- TDO2 represents a promising therapeutic target for the treatment of CRC.
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