BAIAP2L2 facilitates hepatocellular carcinoma progression and immune evasion of via targeting JAK1-mediated pathway and PD-L1 expression.

Abstract

Hepatocellular carcinoma (HCC) poses a serious threat to human health due to its high mortality rate. Recently, breakthrough progress has been made in immunotherapy field. However, the mechanisms underlying HCC progression and immune escape are still unclear. This study aimed to investigate the impact of brain-specific angiogenesis inhibitor 1-associated protein 2-like 2 (BAIAP2L2) in HCC and elucidate its potential mechanisms in this context. Clinical data revealed that the overexpression of BAIAP2L2 correlated with tumor progression and poor prognosis in HCC patients. Functional assays demonstrated that BAIAP2L2 facilitates HCC proliferation, metastasis, invasion, and PD-L1-mediated immune evasion both in vitro and in vivo. Mechanistically, we observed co-localization and interaction between BAIAP2L2 and JAK1 within HCC cells, in turn enhancing the activation of the JAK1/STAT3 signaling pathway. Utilizing the JAK1 inhibitor Ruxolitinib effectively reversed BAIAP2L2-induced cellular processes such as proliferation, migration, invasion, and PD-L1 upregulation. Overall, our results emphasize that BAIAP2L2 plays a crucial role in driving tumor progression and immune evasion in HCC through the JAK1-mediated signaling pathway, thus proposing BAIAP2L2 as a promising therapeutic target for HCC treatment.