SOX4: A potential therapeutic target for liver disease

SOX4, a member of the sex-determining region Y-related high-mobility group box (SOX) transcription factor family, plays a regulatory role in many physiological and pathological functions, including tissue development, stem cell maintenance, cell differentiation, angiogenesis, epithelial–mesenchymal transition, fibrosis, and tumorigenesis, through the transcriptional activation or epigenetic modification of downstream genes. As an oncogene, SOX4 is up-regulated in more than 20 tumor types and can promote tumor development by inhibiting cancer cell apoptosis and promoting cancer cell proliferation, survival, epithelial–mesenchymal transition, angiogenesis, invasion, and metastasis. SOX4 also plays important roles in the liver, for example, by regulating the development of bile ducts, and in liver diseases, SOX4 can exacerbate disease progression by promoting hepatitis B virus replication and inducing hepatic steatosis and hepatocellular carcinoma proliferation and metastasis by affecting various signaling pathways, such as the TGFβ, MAPK, SREBP, p53, and Bax pathways. Although previous studies have investigated the role of the SOX family in liver development and the function of SOX4 in cancer, a comprehensive review elucidating the mechanisms through which SOX4 regulates liver development and disease progression is lacking. This review provides a general overview of the structure and function of SOX4 and a comprehensive summary of its role and mechanism in hepatitis B virus infection, metabolic dysfunction-associated steatotic liver disease, liver fibrosis, and hepatocellular carcinoma, providing new insights into disease treatment and drug development targeting SOX4.