Silencing LY6D Expression Inhibits Colon Cancer in Xenograft Mice and Regulates Colon Cancer Stem Cells'
Jinyue Duan1, Yi Wang1, Yuanyuan Chen1
1Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
Abstract:
This study explored the role of lymphocyte antigen 6 family member D (LY6D) in colon cancer stem cells' (CCSCs) proliferation and invasion. LY6D was knocked down using siRNA, and the down-regulation of LY6D was verified using Western blotting. After LY6D knockdown, CCSCs' proliferation, stemness, and invasion were suppressed, whereas apoptosis was increased. Gene Ontology (GO) enrichment analysis revealed that the differentially expressed genes (DEGs) between siLY6D and the negative control groups were significantly enriched in the cell-substrate adherens junction, focal adhesion, and cell-substrate junction terms. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DEGs were significantly enriched in the MAPK pathway. In addition, Western blotting results showed that pBRAF and pERK1/2, cascade kinases of the MAPK pathway, were significantly down-regulated after LY6D knockdown. In addition, nude mice xenograft experiments showed that the siLY6D treatment decreased tumor sizes and weights and improved tumor-bearing mice survival rates compared with the control group. In conclusion, these findings indicate that LY6D, which is highly expressed in CCSCs, is a key factor involved in tumor growth and development and might be a potential cancer marker and therapeutic target for colon cancer.
Insights
Lymphocyte antigen 6 family member D (LY6D) drives colon cancer stem cell growth and invasion. Inhibiting LY6D suppressed tumor development and improved survival, highlighting LY6D as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Colon cancer stem cells (CCSCs) drive tumor growth and metastasis.
- Identifying key regulators of CCSC function is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of Lymphocyte antigen 6 family member D (LY6D) in colon cancer stem cells (CCSCs).
- To evaluate LY6D as a potential therapeutic target for colon cancer.
Main Methods:
- LY6D knockdown using siRNA and Western blotting for verification.
- Assessment of CCSC proliferation, stemness, invasion, and apoptosis.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
- Western blotting to analyze MAPK pathway kinases.
- Nude mice xenograft experiments to assess in vivo tumor growth.
Main Results:
- LY6D knockdown significantly suppressed CCSC proliferation, stemness, and invasion while increasing apoptosis.
- Enrichment analyses identified cell-substrate junctions and the MAPK pathway as affected by LY6D knockdown.
- LY6D knockdown led to down-regulation of MAPK pathway kinases (pBRAF, pERK1/2).
- In vivo, LY6D inhibition reduced tumor size and weight and improved survival rates in mice.
Conclusions:
- LY6D is highly expressed in CCSCs and plays a critical role in colon tumor growth and development.
- LY6D inhibition demonstrates therapeutic potential by suppressing tumor progression.
- LY6D represents a promising biomarker and therapeutic target for colon cancer treatment.
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