Neuroglobin, a Novel Intracellular Hexa-Coordinated Globin, Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Raf/MAPK/Erk
文献类型：期刊论文
| 作者 | Zhang, J; Lan, SJ; Liu, QR; Liu, JM; Chen, XQ |
| 刊名 | MOLECULAR PHARMACOLOGY
 |
| 出版日期 | 2013 |
| 卷号 | 83期号:5页码:1109-1119 |
| 通讯作者 | Chen, XQ (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathophysiol, Hangkong Rd 13, Wuhan 430032, Peoples R China.,chenxiaoqian66@gmail.com |
| 英文摘要 | Hypoxia and oxidative stress are critical factors in carcinogenesis and exist throughout cancer development; however, the underlying mechanisms are far from clear. Here, for the first time to our knowledge, we reported that neuroglobin (Ngb), an intracellular hexa-coordinated globin serving as an oxygen/reactive oxygen species (ROS) sensor, functions as a tumor suppressor in hepatocelluar carcinoma (HCC). Ngb protein and mRNA expression were significantly down-regulated in tumor tissues, compared with its adjacent non-tumor tissues of human HCC samples and normal liver tissues. Knock-down of Ngb by RNA interference promoted human HCC cell line (HepG2) growth and proliferation, G0/G1-S transition in vitro, and tumor growth in vivo. On the contrary, overexpression of Ngb suppressed HepG2 cell growth and proliferation, G0/G1-S transition, colony formation in vitro, and tumorigenicity in vivo. These results established a tumor suppressor function of Ngb in HCC. The underlying mechanisms were further investigated. Overexpression of Ngb suppressed Raf/MEK/extracellular signal-regulated kinase (Erk), whereas knockdown of Ngb enhanced Raf/MEK/Erk activation in HepG2 cells in vitro and in vivo. Glutathione S-transferase pull-down showed that Ngb interacted with c-Raf-1 in HepG2 cells. Overexpression of Ngb suppressed serum-and H2O2-stimulated Erk activation in HepG2 cells. Pharmacological inhibition of Erk activation abolished the proliferative effect of Ngb knockdown in HepG2 cells. Mutation of Ngb at its oxygen-binding site (H64L) abolished the inhibitory effects of Ngb on Erk activation and HepG2 cell proliferation. Therefore, we propose that Ngb controls HCC development by linking oxygen/ROS signals to oncogenic Raf/mitogen-activated protein kinase (MAPK)/Erk signaling. Our data suggest that neuroglobin could be a new target for cancer therapy. |
| 学科主题 | Pharmacology & Pharmacy |
| 类目[WOS] | Pharmacology & Pharmacy |
| 关键词[WOS] | THERAPEUTIC TARGETS ; MURINE NEUROGLOBIN ; OXIDATIVE STRESS ; NITRIC-OXIDE ; EXPRESSION ; PATHWAYS ; BINDING ; INJURY ; OXYGEN ; PHOSPHORYLATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000317575500019 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/390]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhang, J,Lan, SJ,Liu, QR,et al. Neuroglobin, a Novel Intracellular Hexa-Coordinated Globin, Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Raf/MAPK/Erk[J]. MOLECULAR PHARMACOLOGY,2013,83(5):1109-1119. |
| APA | Zhang, J,Lan, SJ,Liu, QR,Liu, JM,&Chen, XQ.(2013).Neuroglobin, a Novel Intracellular Hexa-Coordinated Globin, Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Raf/MAPK/Erk.MOLECULAR PHARMACOLOGY,83(5),1109-1119. |
| MLA | Zhang, J,et al."Neuroglobin, a Novel Intracellular Hexa-Coordinated Globin, Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Raf/MAPK/Erk".MOLECULAR PHARMACOLOGY 83.5(2013):1109-1119. |
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