EFTUD2 Promotes Cell Survival,Metastasis And Predicts Poor Prognosis In Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma is one of the most common malignant tumors in China.The latest global cancer data shows that the global incidence of liver cancer ranks eighth,and the mortality rate ranks fourth,with male liver cancer ranking among the top three.More than half of all new cases of liver cancer and deaths occur in China every year.In China,the proportion of patients with liver cancer who can be diagnosed early and treated with surgery is only 10%-20%.Most patients are advanced or terminally diagnosed with liver cancer.The treatment is very limited and the prognosis is poor.The development of multiple lesions,intrahepatic or distant metastasis is the main cause of poor prognosis and high recurrence rate after surgical resection of HCC patients.However,the current mechanisms for postoperative recurrence and metastasis of liver cancer and effective control measures remain unclear.Therefore,new predictive indicators need to be discovered to improve the early diagnosis of liver cancer,thereby reducing the mortality rate of liver cancer.Elongation factor Tu GTP binding domain-containing protein(EFTUD2):a core component of U5 small nuclear ribonucleoprotein(U5 snRNP),a highly conserved GTPase involved in catalytic RNA splicing and splicing complexes Dissociation after body splicing.The literature reports that the eftud2 gene mutation can causemandibular dysplasia,head deformity,cleft lip and other head and facemalformations,suggesting that EFTUD2 may be necessary for growth and development.In addition,the study found that EFTUD2 can mediate apoptosis in breast cancer cells and neural precursor cells.The role of EFTUD2 in the development of tumor research has not been reported in detail.In this study,we examined the expression and distribution of EFTUD2 in HCC tissues and its adjacent non-tumor tissues and normal liver tissues,and analyzed the effect of EFTUD2 on survival and prognosis of patients after liver cancer surgery,and further explored the role of EFTUD2 in the development of liver cancer and the underlying molecular mechanisms.Results1.The expression of EFTUD2 in tissue microarray and 126 cases of liver cancer and its corresponding adjacent tissues was analyzed by TCGA database and immunohistochemistry(IHC).The results showed that EFTUD2 was highly expressed in liver cancer,and the expression level was much higher than that of adjacent tissues and normal liver tissue:patients with high expression of EFTUD2,low long-term survival rate,high early recurrence rate,is a predictor of poor prognosis of liver cancer patients;2.The effects of EFTUD2 on the proliferation and apoptosis of hepatoma cells were detected by in vitro cell functional assays such as CCK8,EdU,plate cloning,cell cycle and cell apoptosis.The results showed that down-regulated of EFTUD2 promotes cell apoptosis and growth.conversely,promotes the proliferation of liver cancer cells;3.RNA sequencing showed that EFTUD2 was associated with JAK/STAT3 and EMT signaling pathways.Molecular biology techniques such as immunofluorescence and Western blot showed that EFTUD2 maintained the survival of HCC cells and promoted EMT changes in HCC cells by activating JAK/STAT3 signaling pathway.ConclusionEFTUD2 is significantly up-regulated in HCC tissues and correlates with poor prognosis and high recurrence rates in HCC patients.And EFTUD2 promotes cell survival and metastasis via activating JAK/STAT3 signaling in hepatocellular carcinoma...