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Transcriptome Analysis Reveals Anti-Cancer Effects of Isorhapontigenin (ISO) on Highly Invasive Human T24 Bladder
Alex H Li1, Sun Young Park1, Peiwei Li1
1Division of Environmental Medicine, Department of Medicine, NYU Grossman School of Medicine, 341 East 25th Street, New York, NY 10010, USA.
Abstract:
Bladder cancer, the most common malignancy of the urinary tract, has a poor overall survival rate when the tumor becomes muscle invasive. The discovery and evaluation of new alternative medications targeting high-grade muscle invasive bladder cancer (MIBC) are of tremendous importance in reducing bladder cancer mortality. Isorhapontigenin (ISO), a stilbene derivative from the Chinese herb Gnetum cleistostachyum, exhibits a strong anti-cancer effect on MIBCs. Here, we report the whole transcriptome profiling of ISO-treated human bladder cancer T24 cells. A total of 1047 differentially expressed genes (DEGs) were identified, including 596 downregulated and 451 upregulated genes. Functional annotation and pathway analysis revealed that ISO treatment induced massive changes in gene expression associated with cell movement, migration, invasion, metabolism, proliferation, and angiogenesis. Additionally, ISO treatment-activated genes involved in the inflammatory response but repressed genes involved in hypoxia signaling, glycolysis, the actin cytoskeleton, and the tumor microenvironment. In summary, our whole transcriptome analysis demonstrated a shift in metabolism and altered actin cytoskeleton in ISO-treated T24 cells, which subsequently contribute to tumor microenvironment remodeling that suppresses tumor growth and progression.
Insights
Isorhapontigenin (ISO) shows anti-cancer effects on muscle invasive bladder cancer (MIBC) by altering gene expression. This natural compound shifts cell metabolism and actin cytoskeleton, impacting the tumor microenvironment to suppress growth.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Muscle invasive bladder cancer (MIBC) has a poor prognosis, necessitating novel therapeutic strategies.
- Isorhapontigenin (ISO), a stilbene derivative, demonstrates significant anti-cancer activity against MIBC.
- Identifying molecular targets of ISO is crucial for developing effective bladder cancer treatments.
Purpose of the Study:
- To investigate the molecular effects of Isorhapontigenin (ISO) on human bladder cancer T24 cells using whole transcriptome profiling.
- To identify differentially expressed genes (DEGs) and associated pathways affected by ISO treatment.
- To elucidate the mechanisms by which ISO influences cancer cell behavior and the tumor microenvironment.
Main Methods:
- Whole transcriptome sequencing was performed on human bladder cancer T24 cells treated with ISO.
- Differential gene expression analysis was conducted to identify upregulated and downregulated genes.
- Functional annotation and pathway analysis were used to interpret the biological significance of gene expression changes.
Main Results:
- A total of 1047 differentially expressed genes (DEGs) were identified, with 596 downregulated and 451 upregulated.
- ISO treatment significantly altered gene expression related to cell movement, migration, invasion, metabolism, proliferation, and angiogenesis.
- Key pathways affected include inflammation (activated), hypoxia signaling, glycolysis, actin cytoskeleton, and tumor microenvironment (repressed).
Conclusions:
- ISO treatment induces substantial changes in gene expression in bladder cancer cells, affecting critical cellular processes.
- The observed metabolic shift and altered actin cytoskeleton in ISO-treated cells contribute to tumor microenvironment remodeling.
- These molecular alterations suggest that ISO has the potential to suppress tumor growth and progression in MIBC.
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