Published online Jul 21, 2022. doi: 10.3748/wjg.v28.i27.3435
Peer-review started: February 7, 2022
First decision: April 5, 2022
Revised: April 16, 2022
Accepted: June 3, 2022
Article in press: June 3, 2022
Published online: July 21, 2022
Processing time: 161 Days and 6.1 Hours
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate. The molecular biology research of HCC can reveal the potential mechanism and provide direction for its comprehensive treatment.
The relationship between RING finger and WD repeat domain 3 (RFWD3) and the tumorigenesis process has been reported occasionally; however, the relationship between RFWD3 and HCC is still unclear.
We aimed to investigate the relationship between HCC and RFWD3 and explore the underlying molecular signalling transduction pathways.
We analyzed RFWD3 expression in HCC tissues and evaluated cell phenotypes such as proliferation, apoptosis, migration, and invasion using Lentivirus mediated RFWD3 knockdown. In addition, in vivo experiments were performed to observe tumor growth and metastasis. Next, the phenotype was verified using the lentiviral-mediated rescue of RFWD3 shRNA. Finally, we unraveled the regulatory network underlying HCC using microarray, bioinformatics, and western blot analyses.
RFWD3 expression levels were correlated with tumor size and TNM stage in clinical samples. RFWD3 silencing increased apoptosis, decreased growth, and inhibited migration in HCC cell lines and nude mice, which were resumed with RFWD3 shRNAi rescue. Subsequent experiments revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.
This study shows that RFWD3 affects the Wnt/β-catenin signalling pathway and therefore affects HCC tumorigenesis.
The findings suggest that RFWD3 could be a potential therapeutic target for HCC. However, it warrants further investigations to ascertain these inferences.