Protein acetylation has emerged to play pivotal roles in alcoholic liver disease (ALD). Sirutin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase involved in the regulation of aging, metabolism, and stress. However, the role of SIRT2 in ALD remains unclear. Here, we report that the SIRT2-mediated deacetylation–deubiquitination switch of CCAAT/enhancer-binding protein beta (C/EBPβ) prevents ALD. Our results showed that hepatic SIRT2 protein expression was negatively correlated with the severity of alcoholic liver injury in ALD patients. Liver-specific SIRT2 deficiency sensitized mice to ALD, whereas transgenic SIRT2 overexpression in hepatocytes significantly prevented ethanol-induced liver injury via normalization of hepatic steatosis, lipid peroxidation, and hepatocyte apoptosis. Mechanistically, we identified C/EBPβ as a critical substrate of SIRT2 implicated in ALD. SIRT2-mediated deacetylation at lysines 102 and 211 decreased C/EBPβ ubiquitination, resulting in enhanced protein stability and subsequently increased transcription of C/EBPβ-target gene LCN2. Importantly, hepatic deacetylated C/EBPβ and LCN2 compensation reversed SIRT2 deletion-induced ALD aggravation in mice. Furthermore, C/EBPβ protein expression was positively correlated with SIRT2 and LCN2 expression in the livers of ALD patients and was inversely correlated with ALD development. Therefore, activating SIRT2-C/EBPβ-LCN2 signaling pathway is a potential therapy for ALD.

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As a research hotspot in recent years, bone mesenchymal stem cells (BMSCs) play an important role in the process of a variety of human diseases, including cancers. However, in osteosarcoma, the role of BMSCs and their communication with tumour cells are not clear. In this study, we validated the communication of osteosarcoma (OS) cells with BMSCs. The results showed that the conditioned medium of osteosarcoma cell line U2OS (U2OS-CM) induces the carcinoma-associated fibroblasts (CAFs)-like transformation of BMSCs and promotes the proliferation, migration and invasion of BMSCs. Mechanistically, treatment of human bone mesenchymal stem cells (hBMSCs) with U2OS-CM results in a significant increase in the IL-6 expression and phosphorylation of STAT3. Furthermore, blockade of the IL-6/STAT3 signalling in hBMSCs rescues the transformation of CAF phenotype induced by U2OS-CM. And, human IL-6 can directly increase the expression of the CAF marker genes in hMSCs. Meanwhile, IL-6/STAT3 signalling involves in promoting effects of U2OS-CM on the proliferation, migration and invasion of BMSCs. In summary, our results suggest that BMSCs communicate with OS cells through IL-6/STAT3 signalling and play an important role in the progress of osteosarcoma.