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文章:

I型干扰素(IFN-I)信号通路失调:肝细胞癌(HCC)种族差异的潜在机制

Dysregulation of Type I Interferon (IFN-I) Signaling: A Potential Contributor to Racial Disparity in Hepatocellular Carcinoma (HCC)

原文发布日期:27 August 2023

DOI: 10.3390/cancers15174283

类型: Article

开放获取: 是

 

英文摘要:

African-American (AA)/Black hepatocellular carcinoma (HCC) patients have increased incidence and decreased survival rates compared to non-Hispanic (White) patients, the underlying molecular mechanism of which is not clear. Analysis of existing RNA-sequencing (RNA-seq) data in The Cancer Genome Atlas (TCGA) and in-house RNA-sequencing of 14 White and 18 AA/Black HCC patients revealed statistically significant activation of type I interferon (IFN-I) signaling pathway in AA/Black patients. A four-gene signature of IFN-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors versus White. HCC is a disease of chronic inflammation, and IFN-Is function as pro-inflammatory cytokines. We tested efficacy of ginger extract (GE), a dietary compound known for anti-inflammatory properties, on HCC cell lines derived from White (HepG2), AA/Black (Hep3B and O/20) and Asian (HuH-7) patients. GE exhibited a significantly lower IC50on Hep3B and O/20 cells than on HepG2 and HuH-7 cells. The GE treatment inhibited the activation of downstream mediators of IFN-I signaling pathways and expression of ISGs in all four HCC cells. Our data suggest that ginger can potentially attenuate IFN-I-mediated signaling pathways in HCC, and cells from AA/Black HCC patients may be more sensitive to ginger. AA/Black HCC patients might benefit from a holistic diet containing ginger.

 

摘要翻译: 

与非西班牙裔(白人)患者相比,非洲裔美国人/黑人肝细胞癌患者的发病率更高且生存率更低,其潜在的分子机制尚不明确。通过对癌症基因组图谱中现有RNA测序数据以及14例白人患者和18例非洲裔美国人/黑人患者的内部RNA测序进行分析,发现非洲裔美国人/黑人患者中I型干扰素信号通路存在统计学显著激活。与白人患者相比,非洲裔美国人/黑人肝细胞癌肿瘤中干扰素刺激基因的四基因标志物表达升高。肝细胞癌是一种慢性炎症性疾病,而I型干扰素具有促炎细胞因子功能。我们测试了具有抗炎特性的膳食化合物——姜提取物对源自白人(HepG2)、非洲裔美国人/黑人(Hep3B和O/20)及亚洲(HuH-7)患者的肝细胞癌细胞系的疗效。姜提取物对Hep3B和O/20细胞的IC50显著低于对HepG2和HuH-7细胞。姜提取物处理抑制了所有四种肝细胞癌细胞中I型干扰素信号通路下游介质的激活及干扰素刺激基因的表达。我们的数据表明,姜可能减弱肝细胞癌中I型干扰素介导的信号通路,且源自非洲裔美国人/黑人肝细胞癌患者的细胞可能对姜更敏感。非洲裔美国人/黑人肝细胞癌患者或可从含姜的均衡饮食中获益。

 

原文链接:

Dysregulation of Type I Interferon (IFN-I) Signaling: A Potential Contributor to Racial Disparity in Hepatocellular Carcinoma (HCC)

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