B-cell lymphoma-2-associated transcription factor 1 is overexpressed and contributes to sorafenib resistance in hepatocellular carcinoma
B-cell lymphoma-2-associated transcription factor 1 is overexpressed and contributes to sorafenib resistance in hepatocellular carcinoma
复制标题
B 细胞淋巴瘤 2 相关转录因子 1 过度表达并导致肝细胞癌中索拉非尼耐药
DOI：
10.1111/hepr.13395
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发表时间：
2019
影响因子：
4.2
通讯作者：
ong
中科院分区：
文献类型：
--
作者：
Yu Shijun;Wang Xiao;Dou Ning;Zhou Jun;Gao Yong;Li Y;ong
目的B细胞淋巴瘤2相关转录因子1（BCLAF 1）参与多种生物学过程，包括肿瘤的发生，但其在肝细胞癌（HCC）中的功能和表达尚不清楚，其在HCC中的临床价值尚未明确。通过共聚焦显微镜、透射电镜和western blot分析BCLAF 1对肝癌细胞自噬的影响。体外和体内进行细胞增殖和致瘤性测定。流式细胞术检测肝癌细胞凋亡水平。采用Kaplan-Meier生存法分析肝癌组织中BCLAF 1表达与索拉非尼耐药的相关性。结果肝癌组织中BCLAF 1的表达高于癌旁正常组织，且BCLAF 1表达与肝癌患者肿瘤淋巴结转移分期、分化程度及预后相关。BCLAF 1可以诱导肝癌细胞响应饥饿的自噬，BCLAF 1介导的自噬可以在应激条件下促进细胞增殖并阻止细胞凋亡。动物实验表明BCLAF 1在体内可促进肝癌细胞的致瘤性。结论BCLAF 1是一种潜在的肝癌癌基因，在应激条件下通过诱导自噬维持肿瘤细胞的生长，可作为预测肝癌患者预后和筛选适合索拉非尼治疗的患者的潜在生物标志物。
AimB‐cell lymphoma‐2‐associated transcription factor 1 (BCLAF1) is involved in various biological processes including tumorigenesis, but its function and expression in hepatocellular carcinoma (HCC) is little known, and its clinical value in HCC has not yet been defined.MethodsThe protein level of BCLAF1 in HCC specimens and paired adjacent normal tissues was examined by immunohistochemical staining. The effects of BCLAF1 on autophagy in HCC cells were detected by confocal microscopy, transmission electron microscopy, and western blot analysis. Cell proliferation and tumorigenicity assays were carried outin vitroandin vivo. Flow cytometry assay was used to determine the apoptosis level of HCC cells. The correlation of BCLAF1 and sorafenib resistance in HCC was analyzed by the Kaplan–Meier survival method.ResultsHigh expression of BCLAF1 was found in HCC tissues compared with adjacent normal tissues, and higher BCLAF1 expression was correlated with higher tumor–node–metastasis stage, worse differentiation, and worse prognosis of HCC patients. BCLAF1 could induce autophagy in HCC cells in response to starvation and BCLAF1‐mediated autophagy could enhance cell proliferation and impede cell apoptosis under stress conditions. Animal experiments indicated that BCLAF1 promoted tumorigenicity of HCC cellsin vivo. More importantly, high expression of BCLAF1 might contribute to sorafenib resistance in HCC patients.ConclusionsBCLAF1is a potential oncogene in HCC by inducing autophagy to maintain tumor cell growth in response to stress conditions, and it could serve as a potential biomarker for predicting the prognosis of HCC patients and screening patients who are suitable for sorafenib therapy.