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Expressions of Orphan Nuclear Receptor TR3/Nur77 in Chronic Hepatopathy and Its Clinical Significance.

作者信息

Zeng Yingling, Ye Xiaoguang, Liao Degui, Huang Shizhang, Mao Huinan, Zhao Dezheng, Zeng Huiyan

机构信息

Departments of Preventative Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P. R. China.

Departments of Infectious Diseases, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P. R. China.

出版信息

J Clin Exp Oncol. 2017 Aug;6(4). doi: 10.4172/2324-9110.1000188. Epub 2017 Jun 1.

DOI:10.4172/2324-9110.1000188
PMID:28856167
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5573240/
Abstract

OBJECTIVE

Although great success has been achieved in cancer treatment, current cancer therapies, including anti-tumorigenesis and anti-angiogenesis, still face the problems of insufficient efficacy, resistance and intrinsic refractoriness, in addition to their toxic side effects. There is a demand to identify additional targets that can be blocked to turn off the downstream effects of most, if not all, pathways. Our studies suggest that orphan nuclear receptor TR3 (human)/Nur77 (mouse) is such a target. Most recently, we reported that TR3/Nur77 expression in human hepatic cancer tissues correlates well with tumor progress, suggesting that TR3 is a specific therapeutic target for hepatic cancers. However, the correlation of TR3/Nur77 expression in hepatocellular carcinoma (HCC) with chronic hepatitis has not been studied.

METHODS

The expression of TR3/Nur77 was analyzed in human primary hepatic cancer specimens from patients that have complete medical records with Immunohistochemically staining. The statistical analysis was used to access the significance of TR3 expression in tumor tissues, cirrhosis tissues and chronic hepatitis tissues with and without hepatitis B virus infection (HBV(+) and HBV(-)), which were obtained from para-tumor tissues.

RESULTS

The positive rates of TR3/Nur77 expression in hepatocellular carcinoma, cancerous liver cirrhosis and chronic hepatitis are 66.67%, 30%, and 20%, respectively, which are statistic significant (p<0.05). The positive rates of TR3/Nur77 expression in hepatocellular carcinoma are statistic significant (p<0.05) with 81.25% and 20% in HBV (+) or HBV (-), respectively.

CONCLUSION

The positive expression rate of TR3/Nur77 in hepatocellular carcinoma is higher than that in chronic hepatitis and cirrhosis. The positive rate of TR3/Nur77 expression in hepatocellular carcinoma is higher with HBV infection than that without infection. Our results suggest that TR3/Nur77 plays an important role in the progression of chronic hepatitis, and the occurrence and development of HCC.

摘要

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本文引用的文献

1
Orphan Nuclear Receptor TR3/Nur77 is a Specific Therapeutic Target for Hepatic Cancers.孤儿核受体TR3/Nur77是肝癌的特异性治疗靶点。
J Clin Exp Oncol. 2017 Jun;6(3). doi: 10.4172/2324-9110.1000184. Epub 2017 May 9.
2
Orphan nuclear receptor TR3/Nur77 improves wound healing by upregulating the expression of integrin β4.孤儿核受体TR3/Nur77通过上调整合素β4的表达促进伤口愈合。
FASEB J. 2015 Jan;29(1):131-40. doi: 10.1096/fj.14-257550. Epub 2014 Oct 17.
3
MicroRNAs associated with HBV infection and HBV-related HCC.与乙肝病毒感染及乙肝相关肝癌相关的微小RNA
Theranostics. 2014 Sep 19;4(12):1176-92. doi: 10.7150/thno.8715. eCollection 2014.
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Nur transcription factors in stress and addiction.应激与成瘾中的核仁转录因子。
Front Mol Neurosci. 2013 Dec 2;6:44. doi: 10.3389/fnmol.2013.00044.
5
The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1.血管通透因子组胺和 5-羟色胺通过 TR3/Nur77 诱导血管生成,随后通过血栓素-1使其截短。
Blood. 2013 Mar 14;121(11):2154-64. doi: 10.1182/blood-2012-07-443903. Epub 2013 Jan 11.
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Molecular pathways: the role of NR4A orphan nuclear receptors in cancer.分子通路:NR4A 孤儿核受体在癌症中的作用。
Clin Cancer Res. 2012 Jun 15;18(12):3223-8. doi: 10.1158/1078-0432.CCR-11-2953. Epub 2012 May 7.
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Hepatocellular carcinoma.肝细胞癌。
Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20.
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Orphan nuclear transcription factor TR3/Nur77 regulates microvessel permeability by targeting endothelial nitric oxide synthase and destabilizing endothelial junctions.孤核转录因子 TR3/Nur77 通过靶向内皮型一氧化氮合酶和破坏内皮细胞连接来调节微血管通透性。
Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12066-71. doi: 10.1073/pnas.1018438108. Epub 2011 Jul 5.
9
Inflammation: a role for NR4A orphan nuclear receptors?炎症:NR4A 孤儿核受体的作用?
Biochem Soc Trans. 2011 Apr;39(2):688-93. doi: 10.1042/BST0390688.
10
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.2008 年全球癌症负担估计值:GLOBOCAN 2008。
Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.