IFITM3 Regulates NCAPG Through Phosphorylation to Influence the Invasion and Metastasis of HCC

Abstract

Background: Several studies have demonstrated that the expression of IFITM3 and NCAPG is closely related to the prognosis of various tumors. However, the mechanism of action of these two is not yet clear. In this study, we have explored the mechanism of action of IFITM3 and NCAPG in the promotion of the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: Specimens of liver cancer and adjacent tissues from 55 HCC patients at the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Nanchang University were collected, and the expression of NCAPG and IFITM3 was determined by qRT-PCR and Western blot. Through the analysis of multiple databases, the relationship between IFITM3 and NCAPG was identified and verified by the CO-IP method. Using SiRNA and plasmids to downregulate and up-regulate IFITM3, we observed the expression of STAT3/CDK1, as well as NCAPG mRNA and protein. After downregulating and up-regulating the expression of IFITM3 and NCAPG, the ability of HCC cells to invade and metastasize was determined using a scratch test and Transwell. After using pathway inhibitors and activators, the expression of NCAPG was observed.Results: According to the database, both IFITM3 and NCAPG were highly expressed in Liver hepatocellular carcinoma. We also confirmed that IFITM3 and NCAPG were up-regulated in HCC tissues and cells. Furthermore, the bioinformatics analysis and CO-IP indicated that there was protein interaction between IFITM3 and NCAPG, and that IFITM3 could regulate NCAPG by phosphorylating it. We further confirmed our observations by retrospective experiments. Reuse of pathway inhibitors and activators indicated that IFITM3 could regulate NCAPG through STAT3/CDK1 to promote the invasion and metastasis of HCC. Finally, animal experiments confirmed that our results were also reproducible in vivo. Conclusion: IFITM3 can regulate NCAPG through STAT3/CDK1 to promote the invasion and metastasis of HCC.