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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.

International Journal of Molecular Sciences
|February 10, 2024
PubMed
Summary

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.

Keywords:
actin cytoskeletonbladder cancermetabolic reprogrammingtumor microenvironmentwhole transcriptome analysis

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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.