The impact of Stromal antigen 2 (STAG2) on migration and invasion of Hepatocellular carcinoma

Abstract Stromal antigen2 (STAG2) is involved in metastasis and invasion processes of various cancers, however, the functions of STAG2 in HCC remain unclear. In our study, We evaluated the global mRNA expression levels of STAG2 using the TCGA and GEO databases. By using qRT-PCR, WB, and IHC, the expression level of STAG2 in HCC tissues was determined. We examined the relationships between the expression of STAG2 and the clinicopathological characteristics of HCC. Subsequently, sh-STAG2 HCC cell model was constructed and the alteration of physiologic function of the cells were detected. RNA-seq and molecular docking were used to reveal the STAG2 regulation network. Finally, Using the ROC curve, the STAG2 and its interacting proteins diagnosis value were assessed. The findings showed that the levels of STAG2 expression significantly increased within both HCC tissues and cells. And high STAG2 protein levels were associated with high metastatic tendency. In sh-STAG2 HCC cell model, the cell apoptosis has been promoted, cell proliferation, migration and invasion have been inhibited, and the key proteins of EMT process changed significantly. DEGs of sh-NC vs. sh-STAG2 were enriched in PI3K-AKT, and Focal adhesion signaling pathway, etc. In Focal adhesion pathway, the mRNA expression levels of VAV3-RAC2-PAK5 showed significant change, and all of them have strong binding energy to STAG2. Moreover, the model of STAG2-VAV3 has a greatest diagnosis efficiency for HCC screening. In conclusion, STAG2 could regulate the migration and invasion of HCC through the Focal adhesion pathway, and this process may be closely related to the VAV3-RAC2-PAK5 genes.