TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanaseOACSTPCD

Background:The role of TROVE domain family member 2 (TROVE2) has been well-demonstrated in autoimmune diseases;however, its involvement in liver cancer remains unclear. Therefore, this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma (HCC). Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction. The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting. High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes. Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells. Results:TROVE2 exhibited significant overexpression in liver cancer tissue, correlating with shorter overall survival. Overexpression of TROVE2 facilitated the invasion, metastasis, and epithelial-mesenchymal transition (EMT) process of HCC cells, whereas TROVE2 knock-down restrained migration, invasion, and EMT in these cells. Transcriptome sequencing and bioinformatics analysis identified heparanase (HPSE) as a downstream target protein of TROVE2. Subsequent back-complementation experiments provided evidence that HPSE over-expression promoted TROVE2-mediated prometastasis effects. Moreover, the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3β phosphorylation. Conclusions:TROVE2 facilitated the invasion, migration, and EMT process of HCC cells through phosphorylation of the HPSE/GSK-3β axis, indicating its significance as an important protein in tumor progression.