Aldo-keto Reductase Family 1 Member B 10 Mediates Liver Cancer Cell Proliferation through Sphingosine-1-Phosphate.
Aldo-keto Reductase Family 1 Member B 10 Mediates Liver Cancer Cell Proliferation through Sphingosine-1-Phosphate.
复制标题
醛酮还原酶家族 1 成员 B 10 通过 1-磷酸鞘氨醇介导肝癌细胞增殖
DOI：
10.1038/srep22746
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发表时间：
2016-03-07
影响因子：
4.6
通讯作者：
He S
中科院分区：
文献类型：
--
作者：
Jin J;Liao W;Yao W;Zhu R;Li Y;He S
AKR1B10 通过调节脂肪酸和脂质合成参与肝癌发生。 AKR1B10 抑制导致肿瘤细胞凋亡，其脂质（尤其是磷脂）减少超过 50%，表明 1-磷酸鞘氨醇 (S1P) 等磷脂参与 AKR1B10 的致癌功能。使用共培养系统，我们发现 QSG-7701（人肝细胞）与 HepG2（肝癌细胞系）共培养可增加 QSG-7701 的增殖，其中 AKR1B10-S1P 信号传导起着关键作用。与之前的研究结果一致，原发性肝细胞癌 (PHC) 组织中的 AKR1B10 mRNA 和蛋白水平高于肿瘤周围组织。有趣的是，PHC 组织中的 S1P 水平也高于肿瘤周围组织。通过分析PHC组织中AKR1B10 mRNA表达量与临床数据的相关性，我们发现AKR1B10 mRNA表达量与血清甲胎蛋白（AFP）、肿瘤淋巴结转移（TNM）分期和淋巴结转移相关，但与其他临床病理变量无关。较高的 AKR1B10 mRNA 表达水平与较短的 DFS（无病生存期）和 OS（总生存期）相关，可作为手术切除的 PHC 患者 DFS 和 OS 的独立预测因子。
AKR1B10 is involved in hepatocarcinogenesis via modulation of fatty acid and lipid synthesis. AKR1B10 inhibition results in apoptosis of tumor cells whose lipids, especially phospholipids, were decreased by over 50%, suggesting involvement of phospholipids like sphingosine-1-phosphate (S1P) in AKR1B10’s oncogenic function. Using a co-culture system, we found that co-culture of QSG-7701 (human hepatocyte) with HepG2 (hepatoma cell line) increases QSG-7701’s proliferation, in which AKR1B10-S1P signaling plays a pivotal role. Consistent with previous findings, AKR1B10 mRNA and protein levels were higher in primary hepatocellular carcinoma (PHC) tissues than in peri-tumor tissues. Interestingly, the level of S1P was also higher in PHC tissues than in peri-tumor tissues. After analyzing the correlation between AKR1B10 mRNA expression in PHC tissues and the clinical data, we found that AKR1B10 mRNA expression was associated with serum alpha-fetoprotein (AFP), tumor-node-metastasis (TNM) stage and lymph node metastasis, but not with other clinicopathologic variables. A higher AKR1B10 mRNA expression level is related to a shorter DFS (disease free survival) and OS (overall survival), serving as an independent predictor of DFS and OS in PHC patients with surgical resection.