CCN3 is a therapeutic target relating enhanced stemness and coagulation in hepatocellular carcinoma.
CCN3 is a therapeutic target relating enhanced stemness and coagulation in hepatocellular carcinoma.
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CCN3是与增强肝细胞癌干性和凝血相关的治疗靶点
DOI：
10.1038/s41598-017-14087-4
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发表时间：
2017-10-23
影响因子：
4.6
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Jia Q;Xue T;Zhang Q;Cheng W;Zhang C;Ma J;Bu Y;Yu S;Liu Q
由于转移频率高，肝细胞癌（HCC）患者的总体预后仍然极其糟糕。自 2003 年以来，我们的研究小组探索了转移性 HCC 组织样本的基因表达谱，并发现了 CCN3 的显着上调。然而，CCN3 的作用和精确的病理功能仍然难以捉摸。我们发现CCN3与HCC患者的不良预后、HCC的恶性表型和血管血栓形成相关。我们进一步评估了CCN3在体外和体内的负面作用，并确定骨桥蛋白（OPN）、凝血因子组织因子（TF）和凝血酶是CCN3下游的主导基因，与肝癌细胞干细胞性呈正相关。我们证明，HCC 细胞中过度表达的 CCN3 可提高体内存活率并增加肺转移数量。 OPN 和 TF 水平升高与核因子 κB (NFκB) 和细胞外信号调节激酶 (ERK) 的信号激活相关。我们的研究结果表明，CCN3 是一个潜在的治疗靶点，会影响 OPN 和凝血因子的上调，从而导致 HCC 组织中干性和凝血微环境的增强。
The general prognosis of patients with hepatocellular carcinoma (HCC) remains extremely dismal, due to the high frequency of metastasis. Since 2003, our research group has explored the gene expression profiles of metastasized HCC tissue samples and identified a significant upregulation of CCN3. However, the role and precise pathological function of CCN3 remains elusive. We showed that CCN3 is associated with the poor prognosis of patients with HCC, the malignant phenotype of HCC, and vascular thrombosis. We further evaluated the negative roles of CCN3in vitroandin vivo, and identified osteopontin (OPN), and coagulation factors tissue factor (TF) and thrombin as the leading genes downstream of CCN3, that are positively associated with HCC cell stemness. We demonstrated that overexpressed CCN3 in HCC cells leads to enhanced survival and increased number of pulmonary metastasesin vivo. The elevated levels of OPN and TF were associated with signal activation of nuclear factor κB (NFκB) and extracellular signal-regulated kinases (ERK). Our findings suggest CCN3 is a potential therapeutic target that would affect the upregulation of OPN and coagulation factors, which would lead to an enhanced stemness and blood coagulation microenvironment in HCC tissue.
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DOI：
10.1155/2012/908601
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Jia QA;Ren ZG;Bu Y;Wang ZM;Zhang QB;Liang L;Jiang XM;Zhang QB;Tang ZY
通讯作者：
Tang ZY
影响因子：
13.5
作者：
Dong, Qiong-Zhu;Zhang, Xiao-Fei;Qin, Lun-Xiu
通讯作者：
Qin, Lun-Xiu
影响因子：
11.5
作者：
Zhang, T;Sun, HC;Tang, ZY
通讯作者：
Tang, ZY
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
13.5
作者：
Ke, Ai-Wu;Shi, Guo-Ming;Fan, Jia
通讯作者：
Fan, Jia