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.

印迹位点调节兄弟（BORIS）作为肝细胞癌的特异性指标，表现出表达显着增加。然而，其上游监管网络仍然是个谜。先前的研究表明Hippo通路与肝细胞癌的进展之间存在很强的相关性。众所周知，激活蛋白 1 (AP-1) 经常与 Hippo 通路相互作用。因此，我们试图证明AP-1家族的主要成员Jun和Fos是否参与BORIS表达的调节。生物信息学分析揭示了 BORIS 启动子内存在 Jun 和 Fos 的结合位点。通过一系列过表达和敲低实验，我们证实Jun和Fos具有增强BORIS表达的能力，从而促进肝癌细胞的迁移和侵袭。此外，甲基化特异性 PCR 和亚硫酸氢盐测序PCR 测定表明，Jun 和 Fos 对 BORIS 启动子的去甲基化没有显着影响。然而，荧光素酶报告基因和染色质免疫沉淀实验证实，Jun 和 Fos 可以直接结合 BORIS 启动子，从而增强其转录。总之，这些结果表明Jun和Fos可以通过直接调节BORIS的表达来促进肝细胞癌的发展。这些发现可能为BORIS作为肝细胞癌临床干预的新靶点提供实验证据。