Background

Nuclear receptors (NRs) are crucial transcription factors involved in cell proliferation, metabolism and homeostasis. Through the development of novel genomic approaches, unknown NR functions have recently been uncovered. NR networks derived from gene expression profiles revealed that NRs are tightly linked to human disease and that targeting these links could provide new therapeutic options. MicroRNAs (miRNAs) have known functions as transcriptional regulators of NR function.

Objective

I attempted to construct an NR-miRNA transcriptional network based on genomic data from human cancer.

Methods

I performed comprehensive analysis with genomic data. Correlation, clustering and survival analysis were done to identify the NR and miRNA correlation in cancer.

Results

Correlation analysis of genomic data revealed relationships between the expression levels of several NRs and miRNAs in human cancer. Based on my NR-miRNA correlation data, I found that NR3C1 expression was highly correlated with that of miR-200 in colon cancer. In most cases, miRNAs suppress expression of their target genes. Thus, miRNAs function as negative regulators during transcription. My analysis revealed that the miR-200 expression level is negatively correlated with that of NR3C1, demonstrating that miR-200 is a negative regulator of NR3C1 in colon cancer. It is known that miR-200 is a master regulator of EMT and that NR3C1 has a link with an EMT marker.

Conclusions

Overall, my genomic analysis revealed that the NR3C1 expression level is correlated with that of miR-200 and that this functional relationship might contribute to colon cancer cell survival. Modulating this axis could be a promising target for treating colon cancer patients.

Graphic abstract

中文翻译：

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核受体和 miRNA 的基因组分析确定了 NR3C1/miR-200 轴在结肠癌中的作用

背景

核受体 (NRs) 是参与细胞增殖、代谢和体内平衡的关键转录因子。通过开发新的基因组方法，最近发现了未知的 NR 功能。来自基因表达谱的 NR 网络显示，NR 与人类疾病密切相关，针对这些联系可以提供新的治疗选择。MicroRNAs (miRNAs) 具有作为 NR 功能的转录调节因子的已知功能。

客观的

我试图根据人类癌症的基因组数据构建一个 NR-miRNA 转录网络。

方法

我对基因组数据进行了综合分析。进行相关性、聚类和生存分析以确定癌症中的 NR 和 miRNA 相关性。

结果

基因组数据的相关性分析揭示了人类癌症中几种 NR 和 miRNA 的表达水平之间的关系。根据我的 NR-miRNA 相关数据，我发现 NR3C1 的表达与结肠癌中的 miR-200 的表达高度相关。在大多数情况下，miRNA 会抑制其靶基因的表达。因此，miRNA 在转录过程中起负调节作用。我的分析显示，miR-200 的表达水平与 NR3C1 的表达水平呈负相关，表明 miR-200 是结肠癌中 NR3C1 的负调节因子。已知 miR-200 是 EMT 的主要调节因子，并且 NR3C1 与 EMT 标记有联系。

结论

总的来说，我的基因组分析显示 NR3C1 表达水平与 miR-200 的表达水平相关，这种功能关系可能有助于结肠癌细胞的存活。调节该轴可能是治疗结肠癌患者的有希望的目标。

图形摘要