Identification of Circular RNA-Based Immunomodulatory Networks in Colorectal Cancer.

Identification of Circular RNA-Based Immunomodulatory Networks in Colorectal Cancer.
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结直肠癌中基于环状 RNA 的免疫调节网络的鉴定。

DOI:
10.3389/fonc.2021.779706
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发表时间:
2021
影响因子:
4.7
通讯作者:
Li Z
Li Z
中科院分区:
医学3区
文献类型:
--
作者:
Feng Z;Li L;Tu Y;Shu X;Zhang Y;Zeng Q;Luo L;Wu A;Chen W;Cao Y;Li Z

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环状RNA(circRNA)最近被认为是多种疾病,特别是肿瘤中的中心分子。我们发现源自核糖核酸酶 P RNA 成分 H1 (RPPH1) 的 circRNA 在基因表达综合 (GEO) 数据集中的结直肠癌 (CRC) 样本中高度表达。我们试图鉴定源自 RPPH1 的新 circRNA,并研究它们对 CRC 免疫浸润的竞争性内源 RNA (ceRNA) 和 RNA 结合蛋白 (RBP) 网络的调节。 circRNA 表达谱、miRNA 和 mRNA 数据分别从 GEO 和癌症基因组图谱 (TCGA) 数据集中提取。使用 R 软件和在线服务器工具鉴定差异表达 (DE) RNA,并使用 Cytoscape 构建 circRNA-miRNA-mRNA 和 circRNA-蛋白质网络。使用 GEPIA2 和 TIMER2 在线服务器工具确定了目标基因与免疫浸润之间的关系。揭示了一个 ceRNA 网络,包括 8 个 circRNA、5 个 miRNA 和 6 个 mRNA。此外,还建立了一个包含 8 个 circRNA 和 49 个蛋白质的 circRNA-蛋白质网络。靶向基因 ENOX1、NCAM1、SAMD4A 和 ZC3H10 与 CRC 肿瘤浸润巨噬细胞密切相关。我们分析了来自 RPPH1 的 circRNA 在 CRC 巨噬细胞浸润中竞争内源性 RNA 结合 miRNA 或蛋白质的特征。研究结果指出了结直肠癌新诊断和治疗模式的发展。
Circular RNAs (circRNAs) have been recently proposed as hub molecules in various diseases, especially in tumours. We found that circRNAs derived from ribonuclease P RNA component H1 (RPPH1) were highly expressed in colorectal cancer (CRC) samples from Gene Expression Omnibus (GEO) datasets. We sought to identify new circRNAs derived from RPPH1 and investigate their regulation of the competing endogenous RNA (ceRNA) and RNA binding protein (RBP) networks of CRC immune infiltration. The circRNA expression profiles miRNA and mRNA data were extracted from the GEO and The Cancer Genome Atlas (TCGA) datasets, respectively. The differentially expressed (DE) RNAs were identified using R software and online server tools, and the circRNA–miRNA–mRNA and circRNA–protein networks were constructed using Cytoscape. The relationship between targeted genes and immune infiltration was identified using the GEPIA2 and TIMER2 online server tools. A ceRNA network, including eight circRNAs, five miRNAs, and six mRNAs, was revealed. Moreover, a circRNA–protein network, including eight circRNAs and 49 proteins, was established. The targeted genes, ENOX1, NCAM1, SAMD4A, and ZC3H10, are closely related to CRC tumour-infiltrating macrophages. We analysed the characteristics of circRNA from RPPH1 as competing for endogenous RNA binding miRNA or protein in CRC macrophage infiltration. The results point towards the development of a new diagnostic and therapeutic paradigm for CRC.
黑树莓通过增强结肠上皮和自然杀伤细胞中 Smad4 的表达来抑制结直肠癌。
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