Integrative Modeling of ceRNA–miRNA–lncRNA–TF Networks under Stress: Predicting Non-Canonical Regulatory Outcomes

Much recent work (e.g., Sanchez-Mejias & Tay, 2015; Cantile et al., 2021; Komatsu et al., 2023) explores individual layers of RNA-based gene regulation, but few models integrate the full spectrum of RNA and protein players, especially under stress conditions. Vakulenko et al. (2023) and Acón-Chan et al. (2018) hint at the complexity and adaptability of these networks. This idea proposes developing advanced mathematical models that incorporate ceRNA and lncRNA sponging, miRNA regulation, and feedback with TFs, all while modeling network re-wiring during stress (e.g., heat shock, hypoxia, or DNA damage). Such integrative simulations could predict emergent, non-canonical regulatory behaviors, identify new therapeutic targets, and explain why some miRNAs show unexpected effects in different contexts.

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