ROS-induced voltage-gated ion channel expression and electrophysiological remodeling in malignant human cells

Area of Science:

• Systems Biology
• Computational Biology
• Oncology

Background:

• Environmental stressors like radiation and temperature shifts induce oxidative stress.
• Oxidative stress upregulates voltage-gated ion channel (VGIC) gene expression.
• Reactive oxygen species (ROS) play a key role in cellular signaling pathways.

Purpose of the Study:

• To investigate how ROS modulate calcium signaling and electrophysiological reprogramming.
• To develop a hybrid model integrating electrophysiological simulations and transcriptional feedback.
• To predict tumorigenic transformation using AI models trained on simulated and human data.

Main Methods:

• Hodgkin-Huxley-based electrophysiological simulations.
• Redox-sensitive transcriptional feedback modeling.
• Transformer-Long Short-Term Memory (LSTM) network for prediction.
• Analysis of human datasets (GSE45827).

Main Results:

• Sustained oxidative perturbations shift epithelial cells (MCF-10A) from non-excitable to excitable states.
• Progressive VGIC expression, depolarization, and genomic instability observed with repeated ROS or thermal pulses.
• LSTM model achieved >90% accuracy in predicting tumorigenic transformation.

Conclusions:

• The hybrid modeling framework effectively simulates ROS-induced cellular reprogramming.
• This approach enables simulation-guided drug target identification and AI-assisted screening of compounds.
• The study bridges systems biology and predictive oncology for electrophysiology-based therapeutic design.