LncRNA PTENP1/miR-21/PTEN Axis Modulates EMT and Drug Resistance in Cancer: Dynamic Boolean Modeling for Cell Fates...

Area of Science:

• Molecular Biology
• Cancer Research
• Systems Biology

Background:

• microRNA-21 (miR-21) targets PTEN, promoting cancer's epithelial-to-mesenchymal transition (EMT) and drug resistance.
• PTEN activates PTENP1, a long non-coding RNA that inhibits miR-21, but their dynamics in DNA damage response (DDR) are unclear.

Purpose of the Study:

• To elucidate the dynamic interplay of PTEN, miR-21, and PTENP1 during the DDR.
• To develop a computational model for predicting cellular responses to DDR in various cancers.

Main Methods:

• Constructed a dynamic Boolean network model integrating published literature from multiple cancer types.
• Validated the model against experimental data from breast cancer, hepatocellular carcinoma (HCC), and oral squamous cell carcinoma (OSCC).

Main Results:

• The model accurately predicts DDR progression from intra-S phase to G2 checkpoint, triggering cell cycle arrest, senescence, autophagy, apoptosis, drug resistance, and EMT.
• Identified nine novel feedback loops (eight positive, one negative) mediated by PTEN, influencing DDR cell fate, drug resistance, and EMT.
• Confirmed the roles of PTENP1, miR-21, and PTEN in modulating EMT and drug resistance.

Conclusions:

• The study provides a comprehensive framework for understanding DDR-mediated cellular responses.
• PTEN, miR-21, and PTENP1 represent potential therapeutic targets for enhancing cancer treatment efficacy.