The oncogenic roles of nuclear receptor coactivator 1 in human esophageal carcinoma.
The oncogenic roles of nuclear receptor coactivator 1 in human esophageal carcinoma.
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核受体辅激活因子1在人食管癌中的致癌作用
DOI：
10.1002/cam4.1786
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发表时间：
2018-10
期刊：
影响因子：
4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Wang L;Li W;Li K;Guo Y;Liu D;Yao Z;Lin X;Li S;Jiang Z;Liu Q;Jiang Y;Zhang B;Chen L;Zhou F;Ren H;Lin D;Zhang D;Yeung SJ;Zhang H
核受体辅激活因子1（Nuclear receptor coactivator 1，NCOA1）在雄激素受体（androgen receptor，AR）、雌激素受体α（estrogen receptor α，ER α）和雌激素受体β（estrogen receptor β，ER β）等多种甾体激素受体介导的基因表达调控中发挥重要作用。因此，在多种癌症类型中发现了NCOA1的失调。然而，临床相关性和NCOA 1在人食管鳞状细胞癌（ESCC）的功能作用知之甚少。我们在这项研究中发现，在人食管鳞癌中，NCOA1蛋白和/或mRNA水平升高以及NCOA1基因扩增。由于这些失调导致的NCOA 1水平升高不仅与更具侵袭性的临床病理学参数相关，而且与生存率较差相关。多个ESCC患者队列的结果强烈表明，NCOA 1水平可以作为总生存率的独立预测因子。此外，沉默ESCC细胞中的NCOA 1显著降低增殖、迁移和侵袭。这些发现不仅表明NCOA1在人类ESCC中起重要作用，而且NCOA1的水平也可以作为ESCC的潜在预后生物标志物，靶向NCOA1可能是ESCC治疗的有效策略。
Nuclear receptor coactivator 1 (NCOA1) plays crucial roles in the regulation of gene expression mediated by a wide spectrum of steroid receptors such as androgen receptor (AR), estrogen receptor α (ER α), and estrogen receptor β (ER β). Therefore, dysregulations of NCOA1 have been found in a variety of cancer types. However, the clinical relevance and the functional roles of NCOA1 in human esophageal squamous cell carcinoma (ESCC) are less known. We found in this study that elevated levels of NCOA1 protein and/or mRNA as well as amplification of the NCOA1 gene occur in human ESCC. Elevated levels of NCOA1 due to these dysregulations were not only associated with more aggressive clinic‐pathologic parameters but also poorer survival. Results from multiple cohorts of ESCC patients strongly suggest that the levels of NCOA1 could serve as an independent predictor of overall survival. In addition, silencing NCOA1 in ESCC cells remarkably decreased proliferation, migration, and invasion. These findings not only indicate that NCOA1 plays important roles in human ESCC but the levels of NCOA1 also could serve as a potential prognostic biomarker of ESCC and targeting NCOA1 could be an efficacious strategy in ESCC treatment.
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