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Acute liver injury is a common and serious syndrome caused by multiple factors and unclear pathogenesis. If the injury persists, liver injury can lead to cirrhosis and liver failure and ultimately results in the development of liver cancer. Emerging evidence has indicated that long noncoding RNAs (lncRNAs) play an important role in the development of liver injury. However, the role of antisense Igf2r RNA (Airn) in acute liver injury and its underlying mechanism remain largely unclear. In this study, we show that Airn is upregulated in liver tissue and primary hepatocytes from an acute liver injury mouse model. Consistently, Airn is also overexpressed in serum samples of patients with acute-on-chronic liver failure and is negatively correlated with the Model for End-Stage Liver Disease (MELD) score. Moreover, gene knockout and rescue assays reveal that Airn alleviates CCl

Background Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases. The dysregulation of liver sinusoidal endothelial cell (LSEC) phenotype is a critical early event in the fibrotic process. However, the biological function of lncRNAs in LSEC still remains unclear. Methods The expression level of lncRNA Airn was evaluated in both human fibrotic livers and serums, as well as mouse fibrotic livers. Gain- and loss-of-function experiments were performed to detect the effect of Airn on LSEC differentiation and hepatic stellate cell (HSC) activation in liver fibrosis. Furthermore, RIP, RNA pull-down-immunoblotting, and ChIP experiments were performed to explore the underlying mechanisms of Airn. Results We have identified Airn was significantly upregulated in liver tissues and LSEC of carbon tetrachloride (CCl4)-induced liver fibrosis mouse model. Moreover, the expression of AIRN in fibrotic human liver tissues and serums was remarkably increased compared with healthy controls. In vivo studies showed that Airn deficiency aggravated CCl4- and bile duct ligation (BDL)-induced liver fibrosis, while Airn over-expression by AAV8 alleviated CCl4-induced liver fibrosis. Furthermore, we revealed that Airn maintained LSEC differentiation in vivo and in vitro. Additionally, Airn inhibited HSC activation indirectly by regulating LSEC differentiation and promoted hepatocyte (HC) proliferation by increasing paracrine secretion of Wnt2a and HGF from LSEC. Mechanistically, Airn interacted with EZH2 to maintain LSEC differentiation through KLF2-eNOS-sGC pathway, thereby maintaining HSC quiescence and promoting HC proliferation. Conclusions Our work identified that Airn is beneficial to liver fibrosis by maintaining LSEC differentiation and might be a serum biomarker for liver fibrogenesis.

To reveal whether STARD5 is a potential biomarker for diagnosis and prognosis of HCC. Using gene expression omnibus and the cancer genome atlas (TCGA) to screen differentially expressed genes in HCC and STARD5 was selected by LASSO algorithm. Then, we analyzed the association between STARD5 and clinical characteristics of HCC patients in TCGA and International Cancer Genome Consortium. Meanwhile, the mRNA and protein level of STARD5 was also verified by collecting 87 cases of HCC patients' liver tissues using qRT-PCR and WB. Next, we applied gene set enrichment analysis (GSEA) for pathways analysis of STARD5. Finally, TIMER1.0 and TISIDB were used to explore the correlation of STARD5 with immune cell infiltration. The expression of STARD5 was lower in HCC and negatively correlated with tumor grade (p 0.05), while high expression of STARD5 suggested a better prognosis for HCC patients (p 0.01) and it could be an independent prognostic predictor (p 0.001). Meanwhile, STARD5 also had strong diagnostic accuracy for HCC patients. GSEA revealed that STARD5-related genes were mainly enriched in E2F targets, G2M checkpoint and KRAS signaling. The TIMER1.0 and TISIDB databases found a negative correlation between STARD5 and tumor immune infiltrating cells. STARD5 could be used as a potential target for HCC diagnosis and prognosis.