Jun/Fos promotes migration and invasion of hepatocellular carcinoma cells by enhancing BORIS promoter activity

Abstract

The Brother of the Regulator of Imprinted Sites (BORIS), as a specific indicator of hepatocellular carcinoma, exhibits a significant increase in expression. However, its upstream regulatory network remains enigmatic. Previous research has indicated a strong correlation between the Hippo pathway and the progression of hepatocellular carcinoma. It is well established that the Activator Protein-1 (AP-1) frequently engages in interactions with the Hippo pathway. Thus, we attempt to prove whether Jun and Fos, a major member of the AP-1 family, are involved in the regulation of BORIS expression. Bioinformatics analysis revealed the existence of binding sites for Jun and Fos within the BORIS promoter. Through a series of overexpression and knockdown experiments, we corroborated that Jun and Fos have the capacity to augment BORIS expression, thereby fostering the migration and invasion of hepatocellular carcinoma cells. Moreover, Methylation-Specific PCR and Bisulfite Sequencing PCR assays revealed that Jun and Fos do not have a significant impact on the demethylation of the BORIS promoter. However, luciferase reporter and chromatin immunoprecipitation experiments substantiated that Jun and Fos could directly bind to the BORIS promoter, thereby enhancing its transcription. In conclusion, these results suggest that Jun and Fos can promote the development of hepatocellular carcinoma by directly regulating the expression of BORIS. These findings may provide experimental evidence positioning BORIS as a novel target for the clinical intervention of hepatocellular carcinoma.