The Role And Regulatory Mechanism Of KCTD1 In The Proliferation,Migration And Angiogenesis Of Hepatocellular Carcinoma

Liver cancer is the second most lethal malignancy in the world,consists mainly of hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(i CCA).Currently,most patients with HCC or i CCA have limited response to molecular-targeted therapies.More and more researches have shown that vascular endothelial growth factor(VEGF)plays an important role in tumor angiogenesis,the occurrence and development of malignant tumors.KCTD1 is a gene containing BTB domain that belongs to the KCTD gene family.Previous studies have found that KCTD1 is associated with some important genes in the development and progression of cancer,but its role and clinical significance in the development and progression of liver cancer remain unclear.In this study,WB and IHC analysis were used to detect the expression of KCTD1 in human liver cancer tissues and cell lines.The effects of KCTD1 on proliferation,migration,invasion,tumorigenic ability,and drug susceptibility of liver cancer cell lines were observed by MTT assays,colony formation,Transwell assays,angiogenesis,subcutaneous tumorigenesis,and tail vein assay of tumor metastasis in vivo and in vitro.At the same time,we also investigated the effects of KCTD1 on HUVEC cell proliferation,migration and angiogenesis.The results showed that KCTD1 is highly expressed in liver cancer tissues and HCC cell lines,and the expression level of KCTD1 is positively correlated with the grade of HCC.Overexpression of KCTD1 could enhance HCC proliferation,migration,invasion,angiogenesis in vitro and in vivo,while the knockdown of KCTD1 reversed these effects.Moreover,KCTD1 knockdown can increase the sensitivity of HCC cells to sorafenib.Overexpression of KCTD1 also enhanced HUVEC cell proliferation,migration and angiogenesis.Further experiments showed that KCTD1 can influence the expression of the VEGF/HIF1-α signaling pathway by promoting VEGF signal pathway,thus regulating the growth and metastasis of liver cancer cells.Therefore,this study showed that KCTD1,as an oncogene,may play an important role in the development of HCC.This work will provide a novel research strategy for targeted therapy of liver cancer.In addition,KCTD1 can also be served as a potential marker for clinical detection,treatment,and prognosis of HCC patients,providing new ideas for relevant studies of HCC.