Activation of the Hippo pathway by the MIAT/miR-877-5p/UBN2 axis contributes to keloid formation

Keloid is a prevalent fibroproliferative condition characterized by excessive extracellular matrix (ECM) accumulation and presents a significant clinical challenge. Despite the recognized association of long non-coding RNAs (lncRNAs) with keloid pathogenesis, their specific roles remain undefined. Here, we identified the lncRNA MIAT as markedly upregulated in keloid tissues and human keloid fibroblasts (HKFs) through bioinformatics analysis of GEO datasets (GSE182192) and experimental validation. Functional assays showed that MIAT silencing in HKFs suppressed proliferation, migration, invasion, ECM deposition (α-SMA, COL1, COL2), and promoted apoptosis. MIAT localized in the cytoplasm and acted as a molecular sponge for miR-877-5p, relieving inhibition of UBN2 and promoting its expression. The MIAT/miR-877-5p/UBN2 axis was confirmed by dual-luciferase reporter and RIP assays. Rescue assays demonstrated that miR-877-5p inhibition counteracted the phenotypic changes induced by MIAT knockdown. UBN2 promoted Hippo pathway transcription by binding TEAD2 and facilitating its nuclear translocation, upregulating CTGF and CYR61. Crucially, in a keloid xenograft model, MIAT knockdown suppressed keloid growth, reversed by simultaneous miR-877-5p inhibition, with altered UBN2 protein levels. Collectively, our findings preliminarily indicate that the MIAT/miR-877-5p/UBN2 axis promotes keloid progression partly through Hippo activation, providing new molecular clues for understanding keloid pathogenesis.