Mechanism of MALAT1 in Regulating the Rab25/PI3K/Akt Pathway via miR-125 in a Mouse Model of Psoriasis

Psoriasis, a prevalent and chronic inflammatory skin disorder, lacks a curative therapy largely due to the incomplete understanding of its complex and multifactorial pathogenesis. A growing body of evidence highlights lncRNAs as a focal point in psoriasis research, with specific transcripts driving critical aspects of its immunopathogenesis. The long non-coding RNA MALAT1, frequently dysregulated in psoriatic lesions, has been identified as a key contributor to the disease, with evidence linking its expression to promoting keratinocyte hyperproliferation and inflammatory responses. Consistent with its potential role in pathogenesis, LncRNA-MALAT1 was substantially elevated in psoriatic skin samples, while miR-125 expression was concurrently suppressed. To explore the functional role of LncRNA-MALAT1, we employed an IMQ-induced psoriasis-like mouse model, which recapitulated the dysregulated expression pattern (increased LncRNA-MALAT1, Rab25, PI3K/AKT activity; decreased miR-125). Strikingly, specific knockdown of LncRNA-MALAT1 in vivo markedly alleviated the inflammatory skin manifestations. This phenotypic improvement coincided with a reversal of the molecular signature, namely downregulation of Rab25 and PI3K/AKT signaling and restoration of miR-125 expression. In summary, these findings suggest that LncRNA-MALAT1 may participate in the pathogenesis and progression of psoriasis by activating the Rab25/PI3K/AKT signaling pathway via miR-125, thereby providing a novel therapeutic target for psoriasis treatment.