Hepatitis B Virus Infection Dampens CtIP Expression in Hepatoma Cell.
Hepatitis B Virus Infection Dampens CtIP Expression in Hepatoma Cell.
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乙型肝炎病毒感染抑制肝癌细胞中的 CtIP 表达
DOI：
10.7150/jca.23649
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发表时间：
2018
影响因子：
3.9
通讯作者：
Ye D
中科院分区：
文献类型：
--
作者：
Zhang D;Liu H;Lin J;Ye D
乙肝病毒感染是导致肝细胞癌的主要原因。DNA双链断裂(DSB)修复的异常可能解释了乙肝相关肝细胞癌的发病机制。肿瘤抑制基因CtIP在DSB修复中起关键作用。本研究的目的是探讨乙肝病毒对肝癌细胞DSB修复过程中CtIP表达的影响。选择HepG2.2.15作为乙肝病毒阳性的肝癌细胞株，HepG2作为乙肝病毒阴性的肝癌细胞株。用博莱霉素诱导这两种细胞株的DSB。通过γ-H_2AX检测，博莱霉素处理可引起DSB。DSB后，HepG2和HepG2.2.15的CtIP基因表达均显著上调，且HepG2.2.15的CtIP表达高于DSB前后的HepG2。CtIP蛋白表达与其基因表达模式一致。磷酸化CtIP(p-CtIP，丝氨酸位点)在DSB前的HepG2和HepG2.2.15中甚至低于可检测到的下限。而在DSB后，HepG2.2.15的p-CtIP显著低于HepG2。这些结果提示，乙肝病毒可以通过增强CtIP的表达而抑制其磷酸化，从而干扰CtIP的表达，从而破坏DSB修复途径，从而导致CtIP功能障碍。
Hepatitis B virus (HBV) infection is a leading cause for hepatocellular carcinoma (HCC). Dysregulation of DNA double-strand break (DSB) repair may explain the pathogenesis of HBV-related HCC. Tumor suppressor CtIP plays a critical role in DSB repair. The purpose of present study was to clarify whether HBV affects CtIP expression in DSB repair of hepatoma cell. HepG2.2.15 was selected as the HBV positive hepatoma cell line, while HepG2 as the HBV negative hepatoma cell line. The two cell lines were treated with bleomycin to induce DSB. Bleomycin treatment could result in DSB by γ-H2AX detection. CtIP gene expression was significantly upregulated after DSB in both HepG2 and HepG2.2.15, while CtIP expression of HepG2.2.15 was higher than that observed in HepG2 before and after DSB. CtIP protein expression was the same pattern as its gene expression. Phosphorylated CtIP (p-CtIP, serine site) was even lower than detectable limit in both HepG2 and HepG2.2.15 before DSB. However, p-CtIP of HepG2.2.15 was significantly lower than that of HepG2 after DSB. These results suggest that HBV could interfere CtIP via enhancing its expression while dampening its phosphorylation, which may disrupt DSB repair pathways and implicate CtIP dysfunction in HBV-related HCC.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
影响因子：
16
作者：
Peterson SE;Li Y;Wu-Baer F;Chait BT;Baer R;Yan H;Gottesman ME;Gautier J
通讯作者：
Gautier J
影响因子：
4.3
作者：
Wu, Guikai;Lee, Wen-Hwa
通讯作者：
Lee, Wen-Hwa
人CTIP介导DNA终端切除和双链断裂修复的细胞周期控制。
DOI：
10.1074/jbc.m808906200
发表时间：
2009-04-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huertas P;Jackson SP
通讯作者：
Jackson SP
影响因子：
16
作者：
You Z;Shi LZ;Zhu Q;Wu P;Zhang YW;Basilio A;Tonnu N;Verma IM;Berns MW;Hunter T
通讯作者：
Hunter T