Long non-coding RNA TTN-AS1 promotes acute liver injury in sepsis: A novel potential monitoring and therapeutic target [RNA-Seq]

However, reliable early biomarkers and effective therapeutic targets are still lacking. In this study, we integrated whole-blood transcriptomic sequencing data and Olink inflammation-related proteomics data from SALI patients to identify key regulatory factors.

By integrating weighted gene co-expression network analysis (WGCNA), differential expression profiling, and competing endogenous RNA (ceRNA) network construction, we identified the long non-coding RNA TTN-AS1 as a potential regulatory candidate. Its upregulation in SALI was further validated using a public dataset. Functional validation in a cecal ligation and puncture (CLP) mouse model demonstrated that TTN-AS1 overexpression significantly aggravated liver injury, as evidenced by elevated serum ALT and AST levels (P < 0.001), increased inflammatory cytokines IL-6 and TNF-α (P < 0.001), disrupted liver architecture and aggravated inflammatory infiltration on H&E staining, enhanced expression of apoptosis-related proteins Caspase-3 (P < 0.001) and BAX (P < 0.01), and increased hepatocyte apoptosis indicated by TUNEL assay (P < 0.001).