Multiomics analyses and machine learning of nuclear receptor coactivator 6 reveal its essential role in hepatocellular carcinoma,Cancer Science

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Multiomics analyses and machine learning of nuclear receptor coactivator 6 reveal its essential role in hepatocellular carcinoma
Cancer Science ( IF 4.5 ) Pub Date : 2022-09-10 , DOI: 10.1111/cas.15577
Yinghao Fang ₁ , Yuyan Xu ₂ , Wei Liao ₁ , Tao Ji ₁ , Linyuan Yu ₁ , Longhai Li ₁ , Mingxin Pan ₂ , Dinghua Yang ₁

Affiliation

Nuclear receptor coactivator 6 (NCOA6), a coactivator of numerous nuclear receptors and transcription factors, regulates multiple critical cellular functions. Nuclear receptor coactivator 6 is dysregulated in various cancers, including hepatocellular carcinoma (HCC); however, its role remains largely unknown. Here we reported that NCOA6 was highly expressed in HCC compared to the adjacent liver tissue, and NCOA6 overexpression was significantly correlated with poor HCC prognosis. Experiments revealed that the knockdown of NCOA6 damaged the proliferation, migration, and invasion of HCC cells. Multiomics and immune infiltration analyses showed a close relationship between NCOA6 expression, multiple cancer-related malignant pathways, and the immunosuppressive microenvironment. Finally, we established an effective NCOA6-related microRNA (miRNA) signature to distinguish HCC from hepatitis\liver cirrhosis patients. To the best of our knowledge, this study is the first to provide a comprehensive analysis of NCOA6 expression in HCC. We found that NCOA6 plays an important role in HCC development and has a potential mechanism of action. Establishing an NCOA6-related miRNA signature will help develop novel diagnostic strategies for HCC patients.

中文翻译：

核受体共激活因子 6 的多组学分析和机器学习揭示其在肝细胞癌中的重要作用

核受体共激活因子 6 (NCOA6) 是众多核受体和转录因子的共激活因子，可调节多种关键细胞功能。核受体共激活因子 6 在多种癌症中失调，包括肝细胞癌 (HCC)；然而，它的作用在很大程度上仍然不为人知。在这里，我们报道了与邻近肝组织相比，NCOA6 在 HCC 中高表达，并且 NCOA6 过表达与 HCC 预后不良显着相关。实验表明，NCOA6 的敲低会破坏 HCC 细胞的增殖、迁移和侵袭。多组学和免疫浸润分析显示 NCOA6 表达、多种癌症相关恶性通路和免疫抑制微环境之间存在密切关系。最后，我们建立了一个有效的 NCOA6 相关 microRNA (miRNA) 特征来区分 HCC 与肝炎\肝硬化患者。据我们所知，这项研究首次对 HCC 中的 NCOA6 表达进行了全面分析。我们发现 NCOA6 在 HCC 发展中起着重要作用，并具有潜在的作用机制。建立与 NCOA6 相关的 miRNA 特征将有助于为 HCC 患者开发新的诊断策略。

更新日期：2022-09-10

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