Late Breaking Abstract - Unraveling the Role of lncRNA SYISL: A Key Regulator in Idiopathic Pulmonary Fibrosis Pathogenesis

Emerging evidence demonstrates that long non-coding RNAs (LncRNAs) play a pivotal role in various physiopathological processes involving tissue regeneration and diseases, while the role and mechanism in the context remain incompletely understood. Herein, we demonstrate that LncRNA hSYISL (SYISL homologs in humans) expression is significantly increased in the lung tissues of patients with IPF and inhibition of SYISL attenuated BLM-induced pulmonary fibrosis in mice. SYISL distributes in both nucleus and cytoplasm which regulates epithelial cell differentiation and lung fibroblast activation in distinct signaling pathways. SYISL in nucleus interaction with DSP enhances pro-fibrotic gene expressions and promotes cell differentiation (epithelial-mesenchymal transition) through YAP1 in epithelial cells. SYISL in the cytoplasm of fibroblast, as a ceRNA binding to miR-23a, regulates TRIOBP expression and modulates the transformation of lung fibroblast into myofibroblast. Within the co-culture system, the overexpression of SYISL and the knockdown of DSP in AEC cells significantly amplify aberrant epithelial-mesenchymal crosstalk by regulating the expression of pro-fibrotic genes of fibrolasts. In summary, SYISL exerts variable functions through interactions with different proteins/RNAs in nucleus and cytoplasm of different cells in IPF.