HBx-induced S100A9 in NF-κB dependent manner promotes growth and metastasis of hepatocellular carcinoma cells.
HBx-induced S100A9 in NF-κB dependent manner promotes growth and metastasis of hepatocellular carcinoma cells.
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HBx 诱导的 S100A9 以 NF-κB 依赖性方式促进肝细胞癌细胞的生长和转移。
DOI：
10.1038/s41419-018-0512-2
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发表时间：
2018-05-24
影响因子：
9
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Duan L;Wu R;Zhang X;Wang D;You Y;Zhang Y;Zhou L;Chen W
肝细胞癌（HCC）与乙型肝炎病毒（HBV）感染有关。髓系特异性S100蛋白（S100s），即S100A8、S100A9和S100A12，最近被确认为新发现的损伤相关分子模式（DAMPs），与感染性疾病病原体的进展相关。然而，S100s是否受HBV调控并参与HBV相关的肝癌发生仍不清楚。在此，我们发现髓系特异性S100s（S100A8、S100A9和S100A12）在HCC患者的血清和组织样本中的表达水平均升高。在HBV阳性HCC患者的血清和组织样本中，S100A9的表达高于HBV阴性HCC患者，而S100A8和S100A12则无此差异。在表达1.3倍HBV基因组或HBV编码的X蛋白（HBx）的HepG2细胞以及稳定产生HBV的细胞系HepG2.2.15中，也证实了细胞内和细胞外S100A9水平较高。HBx可促进NF - κB从细胞质向细胞核转位，并且NF - κB与S100A9的启动子结合以增强其转录。沉默S100A9表达在体外和体内均可部分阻断HBx诱导的HepG2细胞的生长和转移。此外，发现血清S100A9水平与HBV相关HCC的TNM分期、肝外转移状态和HBV DNA载量相关，并且对识别肝外转移具有更好的诊断价值。我们的这些数据表明，S100A9在HBx诱导的HCC生长和转移中起关键作用，并可作为肝外转移的潜在诊断标志物。
Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) infection. Myeloid-specific S100 proteins (S100s), namely, S100A8, S100A9 and S100A12, have been recently recognized as newly discovered damage-associated molecular patterns (DAMPs) that are correlated with progression in pathogen of infectious diseases. However, whether S100s are regulated by HBV and involved in HBV-related hepatocarcinogenesis are still unclear. Here, we found that all expression levels of myeloid-specific S100s (S100A8, S100A9 and S10012) were elevated in serum and tissue samples from HCC patients. Expression of S100A9 but not S100A8 and S10012 were also higher in blood serum and tissue samples from HBV-positive HCC patients than that in HBV-negative HCC patients. High levels of intracellular and extracellular S100A9 were also confirmed in HepG2 cells expressing 1.3-fold HBV genome or HBV-encoded X protein (HBx) as well as in a stable HBV-producing cell line HepG2.2.15. HBx was shown to facilitate translocation of NF-κB from the cytoplasm to the nucleus, and NF-κB bound to the promoter of S100A9 to enhance its transcription. Silencing S100A9 expression partially blocked HBx-induced growth and metastasis of HepG2 cells both in vitro and in vivo. Further, serum S100A9 levels were found to correlate with TNM stage, extrahepatic metastasis status and HBV DNA load in HBV-related HCC and also had a better diagnostic value for identifying extrahepatic metastasis. Our these data demonstrate that S100A9 plays a pivotal role in HBx-induced growth and metastasis of HCC and may serve as a potential diagnostic marker for extrahepatic metastasis.
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影响因子：
5.1
作者：
McGlynn KA;Petrick JL;London WT
通讯作者：
London WT
DOI：
10.1097/inf.0b013e31824672cb
发表时间：
2012-03
期刊：
The Pediatric infectious disease journal
影响因子：
--
作者：
Liu K;Pichichero ME
通讯作者：
Pichichero ME
影响因子：
3.7
作者：
Chen B;Miller AL;Rebelatto M;Brewah Y;Rowe DC;Clarke L;Czapiga M;Rosenthal K;Imamichi T;Chen Y;Chang CS;Chowdhury PS;Naiman B;Wang Y;Yang D;Humbles AA;Herbst R;Sims GP
通讯作者：
Sims GP
DOI：
10.1155/2012/172894
发表时间：
2012
期刊：
Pathology research international
影响因子：
--
作者：
Nakagawa H;Maeda S
通讯作者：
Maeda S
乙型肝炎病毒X基因同时诱导肝祖细胞中的细胞增殖和抑制细胞分化。
影响因子：
5.4
作者：
Huang, Jiayi;Shen, Lihong;Song, Fangzhou
通讯作者：
Song, Fangzhou