Probing the Code of Chronic Urticaria Pathogenesis: How the ceRNA Network Regulates Mast Cell Activation

Chronic urticaria (CU) is an inflammatory skin disease characterized by aberrant mast cell (MC) activation. Notably, 30% of patients show poor response to existing therapies. The competitive endogenous RNA (ceRNA) network has emerged as a key regulator of MC signaling, but the hierarchical regulatory mechanisms underlying this process remain incompletely understood.

This review systematically analyzed PubMed and Web of Science literature (2000-2024) using keywords linking CU, ceRNA/long-stranded non-coding RNA/circular RNA, and MCs. It proposes a three-tiered regulatory model of the ceRNA network in maintaining sustained MC activation: (1) core RNAs (e.g., NEAT1) adsorb microRNAs (miRNAs) to deregulate key signaling pathways; (2) shared miRNAs (e.g., miR-155) act as bridges between upstream and downstream targets; and (3) effector molecules (e.g., STAT3) drive MC activation. RNA-based therapeutics and exosome delivery technologies targeting these regulatory axes may offer new strategies for refractory CU.

(1) The ceRNA network orchestrates MC activation through hierarchical regulation of core RNAs, shared miRNAs, and effector molecules. (2) Targeting ceRNA-mediated pathways holds promise for developing precision therapies for CU, particularly in patients unresponsive to conventional treatments. (3) Translational approaches using RNA therapeutics or exosome systems may address therapeutic gaps in refractory cases.