SOX13 Regulates The Stemness Of Hepatocellular Carcinoma

Primary liver cancer includes the tumor of Hepatic parenchymal cells and the tumor of Intrahepatic bile duct cancer,and the incidence of hepatocellular carcinoma is a leading position in the world.Currently,studies have found that a series of malignant features such as tumor recurrence,metastasis and drug resistance are related to a minority group of special tumor cells with stemness in the tumor.The SOX family is an important class of transcription factors involved in the formation and development of embryos,regulating cell differentiation and determining cell fate.It has been reported that SOX2,SOX9 and other SOX family members are involved in the regulation of tumor stemness.Our preliminary work in the laboratory showed that the high expression of SOX13 in human hepatocarcinoma tissues was closely related to recurrence and metastasis,poor postoperative survival and dedifferentiation(unpublished).Therefore,we speculate that the high expression of SOX13 in liver cancer is related to its influence on the sternness of liver cancer cells.In this study,we investigated the effects and the molecular mechanism of SOX 13 on the stemness of liver cancer cells through in vitro cell experiments and in vivo animal experiments.First,we enriched liver cancer stem cells by spheroidal experiments and found that SOX 13 was highly expressed in hepatoma stem cells,suggesting that SOX13 is involved in the regulation of liver cancer stem cells.Then,we constructed the SOX13 knockdown stable hepatocarcinoma cell line,and found that knockdown of SOX13 could significantly reduce the expression of CSCs markers such as c-myc,oct4 and cd24,impair the ability of spheroid formation,and enhance the drug sensitivity of liver cancer cells.Meanwhile,in vivo and in vitro experiments also confirmed that knocking down SOX13 could obviously inhibit the proliferation and tumorigenic ability of liver cancer cells.Next,we investigated molecular mechanisms in SOX13 regulating the stemness of hepatocarcinoma cells.The results showed that SOX13 could bind to TAZ promoter.Knockdown of SOX13 could directly inhibit the transcriptional activation activity of TAZ and downregulate the expression of downstream target genes in TAZ.Our results indicate that SOX13 could affect the self-renewal ability,proliferative capacity,multi-drug resistance and tumorigenicity,and clarify the function and preliminary mechanism of SOX 13 regulating the sternness of liver cancer cells,and enrich the role of SOX 13 in liver cancer.It suggests that SOX 13 may be a potential target for liver cancer treatment.