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Updated: Jun 10, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Microarray analysis points to LMNB1 and JUN as potential target genes for predicting metastasis promotion by
Jiafei Liu1,2,3, Hongjie Yang1,2,3, Peng Li1,2,3
1Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China.
Abstract:
Etoposide is a second-line chemotherapy agent widely used for metastatic colorectal cancer. However, we discovered that etoposide treatment induced greater motility potential in four colorectal cancer cell lines. Therefore, we used microarrays to test the mRNA of these cancer cell lines to investigate the mechanisms of etoposide promoting colorectal cancer metastasis. Differentially expressed genes (DEGs) were identified by comparing the gene expression profiles in samples from etoposide-treated cells and untreated cells in all four colorectal cancer cell lines. Next, these genes went through the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Among the top 10 genes including the upregulated and downregulated, eight genes had close interaction according to the STRING database: FAS, HMMR, JUN, LMNB1, MLL3, PLK2, STAG1 and TBL1X. After etoposide treatment, the cell cycle, metabolism-related and senescence signaling pathways in the colorectal cancer cell lines were significantly downregulated, whereas necroptosis and oncogene pathways were significantly upregulated. We suggest that the differentially expressed genes LMNB1 and JUN are potential targets for predicting colorectal cancer metastasis. These results provide clinical guidance in chemotherapy, and offer direction for further research in the mechanism of colorectal cancer metastasis.
Insights
Etoposide chemotherapy may unexpectedly enhance colorectal cancer metastasis by altering gene expression. Researchers identified LMNB1 and JUN as potential biomarkers for predicting this increased cancer cell motility.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Etoposide is a chemotherapy drug used for metastatic colorectal cancer.
- This study investigated the unexpected finding that etoposide treatment can increase colorectal cancer cell motility.
Purpose of the Study:
- To explore the molecular mechanisms by which etoposide promotes colorectal cancer metastasis.
- To identify potential biomarkers for predicting etoposide-induced cancer cell motility.
Main Methods:
- Microarray analysis of mRNA expression in four colorectal cancer cell lines after etoposide treatment.
- Differential gene expression analysis, Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and KEGG Pathway analysis.
- Interaction analysis of differentially expressed genes using the STRING database.
Main Results:
- Etoposide treatment significantly altered gene expression, downregulating cell cycle, metabolism, and senescence pathways.
- Necroptosis and oncogene pathways were significantly upregulated post-etoposide treatment.
- Eight interacting genes (FAS, HMMR, JUN, LMNB1, MLL3, PLK2, STAG1, TBL1X) were identified among the top differentially expressed genes.
Conclusions:
- The study suggests that etoposide can promote colorectal cancer metastasis.
- LMNB1 and JUN gene expression are proposed as potential predictive biomarkers for colorectal cancer metastasis.
- Findings offer clinical guidance for chemotherapy and direct future research into metastasis mechanisms.
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