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

ABSTRACT: Sepsis-associated liver injury (SALI) is a common and severe complication of sepsis that significantly affects patient outcomes. 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). This is the earliest report demonstrating that lncRNA TTN-AS1 contributes to the pathogenesis of SALI, highlighting its promise as a biomarker for early diagnosis and a potential target for therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE301818 | GEO | 2026/07/04

REPOSITORIES: GEO

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

Project description:Sepsis-associated liver injury (SALI) is a common and severe complication of sepsis that significantly affects patient outcomes. 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). This is the earliest report demonstrating that lncRNA TTN-AS1 contributes to the pathogenesis of SALI, highlighting its promise as a biomarker for early diagnosis and a potential target for therapy.

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