Bcl-2 相关转录因子-1 (BCLAF1) 是一种至关重要的细胞凋亡调节蛋白，协调各种恶性肿瘤的进展。这项研究揭示了肝细胞癌 (HCC) 患者中 BCLAF1 表达增加，其中 BCLAF1 水平升高与肿瘤分级升级和生存率降低有关。此外，新的 BCLAF1 表达在对 atezolizumab 和贝伐珠单抗联合治疗不敏感的 HCC 患者中尤其增加，但在患有对联合方案有反应的肿瘤的患者中则没有。值得注意的是，BCLAF1的过度表达会增加体外和体内HCC细胞的增殖，而来自过度表达BCLAF1的细胞的条件培养基显着增强人脐静脉内皮细胞的管形成能力。此外，令人信服的证据表明，根据蛋白质印迹法测定，BCLAF1 可减弱脯氨酰羟化酶结构域蛋白 2 (PHD2) 的表达，并在常氧条件下控制缺氧诱导因子 1α (HIF-1α) 的稳定性，而不会对转录产生任何影响。和 RT-qPCR 分析。随后，采用免疫共沉淀和免疫荧光，我们验证了 BCLAF1 和 Cullin 3 (CUL3) 之间的相互作用，通过这种相互作用，BCLAF1 主动上调 PHD2 的泛素化和降解。 Western blot 和 RT-qPCR 结果表明程序性死亡配体-1 (PD-L1) 是 HCC 中 HIF-1α 的下游反应物之一。因此，我们揭示了 BCLAF1 在促进 PD-L1 转录中的关键作用，并通过与 CUL3 结合，促进常氧条件下 HIF-1α 的积累，从而促进 PHD2 的泛素化和降解。© 2023。 ）。

Bcl-2-associated transcription factor-1 (BCLAF1), an apoptosis-regulating protein of paramount significance, orchestrates the progression of various malignancies. This study reveals increased BCLAF1 expression in hepatocellular carcinoma (HCC) patients, in whom elevated BCLAF1 levels are linked to escalated tumor grades and diminished survival rates. Moreover, novel BCLAF1 expression is particularly increased in HCC patients who were not sensitive to the combined treatment of atezolizumab and bevacizumab, but not in patients who had tumors that responded to the combined regimen. Notably, overexpression of BCLAF1 increases HCC cell proliferation in vitro and in vivo, while the conditioned medium derived from cells overexpressing BCLAF1 strikingly enhances the tube-formation capacity of human umbilical vein endothelial cells. Furthermore, compelling evidence demonstrates that BCLAF1 attenuates the expression of prolyl hydroxylase domain protein 2 (PHD2) and governs the stability of hypoxia-inducible factor-1α (HIF-1α) under normoxic conditions without exerting any influence on transcription, as determined by Western blot and RT‒qPCR analyses. Subsequently, employing coimmunoprecipitation and immunofluorescence, we validated the reciprocal interaction between BCLAF1 and Cullin 3 (CUL3), through which BCLAF1 actively upregulates the ubiquitination and degradation of PHD2. The Western blot and RT‒qPCR results suggests that programmed death ligand-1 (PD-L1) is one of the downstream responders to HIF-1α in HCC. Thus, we reveal the pivotal role of BCLAF1 in promoting PD-L1 transcription and, through binding to CUL3, in promoting the accumulation of HIF-1α under normoxic conditions, thereby facilitating the ubiquitination and degradation of PHD2.© 2023. The Author(s).