The μ-opioid receptor (MOR) promotes tumor initiation in hepatocellular carcinoma
The μ-opioid receptor (MOR) promotes tumor initiation in hepatocellular carcinoma
复制标题
mu-阿片受体（MOR）促进肝细胞癌的肿瘤发生
DOI：
10.1016/j.canlet.2019.03.038
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Guo, Xiangyang
中科院分区：
文献类型：
--
作者：
Li, Yi;Li, Gang;Guo, Xiangyang
肝细胞癌是肝癌中最常见的亚型。麻醉方案可能会影响癌症的发展。寻找新的、有效的肝癌靶点是当前肿瘤治疗的热点。我们先前进行的一项研究表明，增强mU-阿片受体(MOR)的表达促进了细胞的增殖、黏附、迁移和肿瘤的发生。本研究探讨MOR是否调节肝细胞癌干细胞(HCSCs)的自我更新。我们利用细胞功能分析、siRNA、shRNA、流式细胞仪分选和其他分子生物学技术来实现这一目的。结果表明，MOR的表达与肝癌的进展呈正相关。沉默MOR在体外和体内都能显著减少与肝癌相关的肿瘤发生，并显著延长荷瘤小鼠的生存时间。此外，MOR沉默将极大地减少肝癌细胞的克隆形成，表明下调了对肿瘤启动的调控。综上所述，这些结果表明，MOR可作为一种新的可靠的HCSC标志物，并通过MOR-NFAT信号通路成为治疗肝癌的潜在靶点。
Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer. Anesthetic regimens possibly influence cancer development. Exploration of novel, effective targets for liver cancer is the current hotspot in cancer treatment. A previous study conducted by us has demonstrated that enhanced expression of the mu-opioid receptor (MOR) promotes cell proliferation, adhesion, migration, and tumorigenesis. The current study investigates whether MOR regulates self-renewal of hepatocellular carcinoma stem cells (HCSCs). We utilize cell function assays, siRNA, shRNA, flow cytometry sorting, and other molecular biology techniques for this purpose. The results indicate that MOR expression is positively related to hepatocarcinoma progression. Silencing MOR greatly reduce HCC-related tumorigenesis both in vitro and in vivo and significantly extend the survival of tumor-bearing mice. Moreover, MOR silencing will greatly reduce colony formation by HCC cells, indicating down regulation of cancer initiation. In conclusion, these results establish that MOR can be a novel and reliable HCSC marker and a potential therapeutic target against HCC via MOR-NFAT signaling.