Affiliation:
1. The First Affiliated Hospital of Xi'an Jiaotong University
2. Xi'an Jiaotong University
Abstract
Abstract
Bcl-2-associated transcription factor-1 (Bclaf1), an apoptosis-regulating protein of paramount significance, orchestrates the progression of various malignancies. This inquiry reveals the heightened expression of Bclaf1 in hepatocellular carcinoma (HCC) patients, where its elevated levels are conspicuously linked to escalated tumor grades and diminished survival rates. Moreover, novel Bclaf1 exhibits a surge in expression within HCC patients who were not sensitive to the combined treatment of atezolizumab and bevacizumab in contrast to patients who chose such regiment and tumors got weak. Notably, the overexpression of Bclaf1 profoundly fosters HCC cell proliferation in vitro and in vivo, while the conditioned medium derived from these overexpressing cells strikingly enhances the tube-formation capacity of human umbilical vein endothelial cells (HUVECs). 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 blotting and RT-qPCR analyses. Subsequently, employing Co-Immunoprecipitation, we validate the reciprocal interaction between Bclaf1 and Cullin 3 (CUL3), whereby Bclaf1 actively up-regulates the ubiquitination and degradation of PHD2. Western Blot and RT-qPCR analyses suggest that programmed death ligand-1(PDL1) is one of the downstream responders to HIF-1α in HCC. In conclusion, this groundbreaking investigation unveils the pivotal role of Bclaf1 in promoting PDL1 transcription,and in promoting the accumulation of HIF-1α under normoxic conditions through its binding to CUL3, thereby facilitating the ubiquitination and degradation of PHD2.
Publisher
Research Square Platform LLC
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