Sec62 promotes pro-angiogenesis of hepatocellular carcinoma cells under hypoxia

This study aimed to investigate the underlying molecular pathogenic mechanism of Sec62 in hepatocellular carcinoma (HCC). Microarray analysis was conducted to profile the global gene expression in the HCC cell line Huh7 cells transfected with Sec62(high) vs. NC and Sec62(low) vs. NC. Ingenuity pathway analysis and gene set enrichment analysis were used to perform Sec62-related signaling pathway analysis from screened differentially expressed genes (DEGs). A protein-protein interaction network was constructed. Experimental validation of the expression of key DEGs was conducted. Hypoxia-induced tube formation was undertaken to investigate the role of Sec62 in angiogenesis. A total of 74 intersected DEGs were identified from Huh7 cells with Sec62(high) vs. NC and Sec62(low) vs. NC. Among them, 65 DEGs were correlated with the expression of Sec62. The P53 signaling pathway was found to be enriched in Huh7 cells with Sec62(high) vs. NC, while the acute phase response signaling pathway was enriched in Huh7 cells with Sec62(low) vs. NC. DEGs, such as serine protease inhibitor E (SERPINE) and tumor necrosis factor receptor superfamily, member 11B (TNFRSF11B), were not only identified as the lead genes of these enriched pathways, but were also found to be closely related to Sec62. Moreover, knockdown of Sec62 decreased the expression of SERPINE1 (plasminogen activator inhibitor type 1 (PAI-1)) and TNFRSF11B, whereas overexpression of Sec62 had the opposite effects. In addition, knockdown of Sec62 inhibited hypoxia-induced tube formation via PAI-1. Sec62 promoted pro-angiogenesis of HCC under hypoxia by regulating PAI-1, and it may be a crucial angiogenic switch in HCC.

Automated summary

This study investigated the role of Sec62 in hepatocellular carcinoma (HCC) and found that Sec62 may play a crucial role in HCC development and angiogenesis by regulating key genes and signaling pathways. Knockdown of Sec62 decreased the expression of key genes related to angiogenesis, while overexpression of Sec62 had the opposite effects. Additionally, Sec62 promoted pro-angiogenesis of HCC under hypoxia by regulating specific genes, suggesting it as a potential angiogenic switch in HCC.