miR-206 orchestrates breast cancer radiosensitivity through a SIRT1/p53 feedback loop: a network medicine modelling study
Year: 2026
Type: article
Abstract: BACKGROUND: Radiotherapy remains a cornerstone of breast cancer treatment, yet radioresistance limits its efficacy. miR-206 acts as a tumor suppressor by inhibiting SIRT1 and stabilizing p53. However, how these molecular components are organized within larger regulatory networks, and whether such network-level hubs can be therapeutically prioritized, remains unclear. RESULTS: Network modeling predicted a previously unrecognized double-negative feedback loop (miR-206 ⊣ SIRT1 ⊣ p53 → miR-206) that functions as a predicted bistable switch, driving mutually exclusive commitment to either a radiosensitive (apoptotic) or a radioresistant (proliferative) fate. Monte Carlo simulations revealed that opposite perturbations of this circuit consistently drove the system toward the corresponding stable attractor. Edge disruption analysis identified the miR-206/SIRT1 and p53/miR-206 interactions as essential for maintaining bistability, while ATM exerted p53-dependent context-specific effects. Model predictions were consistent with independent experimental observations that miR-206 overexpression suppresses SIRT1, enhances p53 acetylation, and increases radiosensitivity. CONCLUSIONS: This network medicine framework identifies the miR-206/SIRT1/p53 bistable switch as a key regulatory module governing cell-fate decisions in breast cancer radioresistance. The model provides a systems-level platform for prioritizing experimentally testable therapeutic strategies to overcome radioresistance.
Source: BMC Bioinformatics
Institution: Universidade Federal do Rio Grande do Norte
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,990
OpenAlex ID: W7172402364