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μ-阿片受体(MOR)促进肝癌的肿瘤起始。

The μ-opioid receptor (MOR) promotes tumor initiation in hepatocellular carcinoma.

机构信息

Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, China.

Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Cancer Lett. 2019 Jul 1;453:1-9. doi: 10.1016/j.canlet.2019.03.038. Epub 2019 Mar 27.

Abstract

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 μ-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.

摘要

肝细胞癌(HCC)是最常见的肝癌亚型。麻醉方案可能会影响癌症的发展。探索肝癌的新型有效靶点是癌症治疗的当前热点。我们之前的一项研究表明,μ-阿片受体(MOR)的表达增强促进了细胞增殖、黏附、迁移和肿瘤发生。本研究旨在探讨 MOR 是否调节肝癌干细胞(HCSC)的自我更新。为此,我们使用细胞功能测定、siRNA、shRNA、流式细胞术分选和其他分子生物学技术。结果表明,MOR 表达与肝癌的进展呈正相关。沉默 MOR 可显著减少体外和体内与 HCC 相关的肿瘤发生,并显著延长荷瘤小鼠的存活时间。此外,MOR 沉默会大大降低 HCC 细胞的集落形成,表明对癌症起始的下调。总之,这些结果表明,MOR 可以作为一种新型、可靠的 HCSC 标志物,并通过 MOR-NFAT 信号通路成为治疗 HCC 的潜在靶点。

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