HNF4A-BAP31-VDAC1 轴同步调节胃癌中的细胞增殖和铁死亡。
HNF4A-BAP31-VDAC1 axis synchronously regulates cell proliferation and ferroptosis in gastric cancer.
机构信息
Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Department of Oncology, Ren ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
出版信息
Cell Death Dis. 2023 Jun 9;14(6):356. doi: 10.1038/s41419-023-05868-z.
B cell receptor associated protein 31 (BAP31) is closely associated with tumor progression, while the role and mechanism of BAP31 in gastric cancer (GC) remains unknown. This study explored that BAP31 was upregulated in GC tissues and high expression indicated poor survival of GC patients. BAP31 knockdown inhibited cell growth and induced G1/S arrest. Moreover, BAP31 attenuation increased the lipid peroxidation level of the membrane and facilitated cellular ferroptosis. Mechanistically, BAP31 regulated cell proliferation and ferroptosis by directly binding to VDAC1 and affected VDAC1 oligomerization and polyubiquitination. HNF4A was bound to BAP31 at the promoter and increased its transcription. Furthermore, knockdown of BAP31 inclined to make GC cells vulnerable to 5-FU and ferroptosis inducer, erastin, in vivo and in vitro. Our work suggests that BAP31 may serve as prognostic factor for gastric cancer and act as potential therapeutic strategy for gastric cancer.
B 细胞受体相关蛋白 31（BAP31）与肿瘤进展密切相关，但其在胃癌（GC）中的作用和机制尚不清楚。本研究探讨了 BAP31 在 GC 组织中上调，高表达提示 GC 患者生存不良。BAP31 敲低抑制细胞生长并诱导 G1/S 期阻滞。此外，BAP31 衰减增加了膜的脂质过氧化水平，并促进了细胞铁死亡。机制上，BAP31 通过直接与 VDAC1 结合来调节细胞增殖和铁死亡，并影响 VDAC1 寡聚化和多泛素化。HNF4A 在启动子上与 BAP31 结合并增加其转录。此外，BAP31 的敲低使 GC 细胞在体内和体外更容易受到 5-FU 和铁死亡诱导剂 erastin 的影响。我们的工作表明，BAP31 可能是胃癌的预后因素，并可能成为胃癌的潜在治疗策略。
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