TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase

Abstract

Abstract 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 knockdown 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 overexpression 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.