HBx公司
生物
基因敲除
癌症研究
肝细胞癌
下调和上调
转录因子
乙型肝炎病毒
免疫系统
病毒学
信使核糖核酸
六氯环己烷
癌变
病毒
乙型肝炎
肿瘤进展
转移
泛素
抄写(语言学)
RNA干扰
分子生物学
PD-L1
蛋白质降解
免疫逃逸
打开阅读框
结合蛋白
自噬
肝炎
生长因子
信号转导
免疫学
作者
Wenbiao Chen,Chenhong Lin,Luo-lin Wang,Zhi-chao Yu,Yuxiuxiu Xu,Min-Hai Zhang,Lisheng Wang,Jun Yao,Wenbiao Chen,Chenhong Lin,Luo-lin Wang,Zhi-chao Yu,Yuxiuxiu Xu,Min-Hai Zhang,Lisheng Wang,Jun Yao
出处
期刊:Oncogene
[Springer Nature]
日期:2025-11-14
卷期号:44 (48): 4747-4762
标识
DOI:10.1038/s41388-025-03625-4
摘要
Hepatocellular carcinoma (HCC) is a common and serious type of malignant tumor with an unfavorable prognosis, partly attributed to the prevalence of hepatitis B virus (HBV) infection. However, the molecular mechanism underlying HBV-HCC are not yet fully understood. Here, we found that Kruppel-like factor 16 (KLF16) was significantly upregulated in HBV-HCC and KLF16 knockdown suppressed the growth and metastasis of HBV-infected HCC cells. Hepatitis B virus X protein (HBx)-mediated N6-methyladenosine (m6A) modification of KLF16 mRNA promoted the binding of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and IGF2BP3, thereby enhancing the stability of KLF16 mRNA. Furthermore, KLF16 was found to promote the transcription of chromosome 12 open reading frame 49 (C12orf49), which in turn increased programmed death-ligand 1 (PD-L1) expression by competitively binding to speckle-type POZ protein (SPOP) and blocking SPOP-mediated ubiquitination and degradation of PD-L1. HBx contributed to immune escape in HBV-HCC through the KLF16-C12orf49-PD-L1 axis. Importantly, inhibiting KLF16 significantly improved the efficacy of anti-PD-L1 therapy in HBV-HCC. Collectively, our study reveals the newly identified HBx-KLF16-C12orf49-PD-L1 axis and its role in promoting growth and immune evasion in HBV-HCC, offering a promising target for clinical interventions in HBV-HCC treatment.
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