Fam134b (JK‐1, RETREG1) was first identified as an oncogene in esophageal squamous cell carcinoma. However, the roles of FAM 134B during tumorigenesis of hepatocellular carcinoma ( HCC ) and in epithelial‐to‐mesenchymal transition ( EMT ) were previously unclear. In this study, we investigated the function of FAM 134B in HCC and the related tumorigenesis mechanisms, as well as how FAM 134B induces EMT . We detected the expression of FAM 134B in a normal hepatic cell line, HCC cell lines, fresh specimens, and a HCC tissue microarray. A retrospective study of 122 paired HCC tissue microarrays was used to analyze the correlation between FAM 134B and clinical features. Gain‐ and loss‐of‐function experiments, rescue experiments, Akt pathway activator/inhibitors, nude mice xenograft models, and nude mice lung metastasis models were used to determine the underlying mechanisms of FAM 134B in inducing tumorigenesis and EMT in vitro and in vivo . The expression level of FAM 134B was highly elevated in HCC , as compared with that in normal liver tissues and normal hepatic cells. Overexpression of FAM 134B was significantly associated with tumor size ( P = 0.025), pathological vascular invasion ( P = 0.026), differentiation grade ( P = 0.023), cancer recurrence ( P = 0.044), and portal vein tumor thrombus ( P = 0.036) in HCC . Patients with high expression of FAM 134B had shorter overall survival and disease‐free survival than patients with non‐high expression of FAM 134B. Furthermore, knockdown of FAM 134B with sh RNA s inhibited cell growth and motility, as well as tumor formation and metastasis in nude mice, all of which were promoted by overexpression of FAM 134B. Our study demonstrated that Fam134b is an oncogene that plays a crucial role in HCC via the Akt signaling pathway with subsequent glycogen synthase kinase‐3β phosphorylation, accumulation of β‐catenin, and stabilization of Snail, which promotes tumorigenesis, EMT , and tumor metastasis in HCC .

Fatty acid binding protein 5 (FABP5) is mainly involved in the uptake, transport, and metabolism of fatty acid in the cytoplasm, and its role in immune cells has been recognized in recent years. However, the role of FABP5 in macrophage inflammation and its underlying mechanisms were not fully addressed. In our study, the acute liver injury and sepsis mouse models were induced by i.p. injection of LPS and cecal contents, respectively. Oleic acid (0.6 g/kg) was injected four times by intragastric administration every week, and this lasted for 1 wk before the LPS or cecal content challenge. We found that myeloid-specific deletion of FABP5 mitigated LPS-induced acute liver injury with reduced mortality of mice, histological liver damage, alanine aminotransferase, and proinflammatory factor levels. Metabolic analysis showed that FABP5 deletion increased the intracellular unsaturated fatty acids, especially oleic acid, in LPS-induced macrophages. The addition of oleic acid also decreased LPS-stimulated macrophage inflammation in vitro and reduced acute liver injury in LPS-induced or cecal content–induced sepsis mice. RNA-sequencing and molecular mechanism studies showed that FABP5 deletion or oleic acid supplementation increased the AMP/ATP ratio and AMP-activated protein kinase (AMPK) activation and inhibited the NF-κB pathway during the inflammatory response to LPS stimulation of macrophages. Inhibiting AMPK activation or expression by chemical or genetic approaches significantly rescued the decreased NF-κB signaling pathway and inflammatory response in LPS-treated FABP5-knockout macrophages. Our present study indicated that inhibiting FABP5 or supplementation of oleic acid might be used for the treatment of sepsis-caused acute liver injury.