RING finger and WD repeat domain 3 regulates proliferation and metastasis through the Wnt/β-catenin signalling pathways in hepatocellular carcinoma
作者机构:Department of Hepatobiliary and Pancreatic SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Physical ExaminationThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina
出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))
年 卷 期:2022年第28卷第27期
页 面:3435-3454页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:Supported by National Natural Science Foundation of China,No.82172944 and No.81900558 Co-operation Research Plan of Medical Science and Technology of Henan Province,No.LHGJ20190149 the Key Scientific Research Projects of Universities of Henan Province,No.21A320052
主 题:RING finger and WD repeat domain 3 Hepatocellular carcinoma Invasion Proliferation Metastasis Wnt/β-catenin signaling pathways
摘 要:BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research *** abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and *** studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in *** To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction *** RFWD3 gene expression was analyzed in HCC tissues and adjacent normal *** was used to stably knockdown RFWD3 expression in HCC cell *** verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and ***,cell migration and invasion were assessed by wound healing and transwell *** addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and ***,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the ***,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying *** Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P0.05),which indicated a poor prognosis ***3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and ***,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis