Dept. of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Dept. of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Comput Biol Chem. 2020 Dec;89:107370. doi: 10.1016/j.compbiolchem.2020.107370. Epub 2020 Sep 7.
Colorectal cancer (CRC) is one of the most frequent and diagnosed diseases. Accumulating evidences showed that mRNAs and noncoding RNAs play important regulatory roles in tumorigenesis. Identification and determining the relationship between them can help diagnosis and treatment of cancer.
Here we analyzed three microarray datasets; GSE110715, GSE32323 and GSE21510, to identify differentially expressed lncRNAs and mRNAs in CRC. The adjusted p-value ≤0.05 was considered statistically significant. Gene set enrichment analysis was carried out using DAVID tool. The miRCancer database was searched to obtain differentially expressed miRNAs in colorectal cancer, and the miRDB database was used to attain the targets of the obtained miRNAs. To predict the lncRNA-miRNA interactions we used DIANA-LncBase v2 and RegRNA 2.0. Finally the lncRNA-miRNA-mRNA-signaling pathway network was constructed using Cytoscape v3.1.
By analyzing the three datasets, a total of 21 mRNAs (15 up- and 6 down-regulated) and 24 lncRNAs (18 up- and 6 down-regulated) were identified as common differentially expressed genes between CRC tumor and marginal tissues. Nevertheless, the constructed lncRNA-miRNA-mRNA-signaling pathway network revealed a convergence on 6 lncRNAs (3 up- and 3 downregulated), 7 mRNAs (2 up- and 5 downregulated) and 6 miRNAs (3 up- and 3 downregulated). We found that dysregulation of lncRNAs such as PCBP1-AS1, UCA1 and SNHG16 could sequester several miRNAs such as hsa-miR-582-5p and hsa-miR-198 and promote the proliferation, invasion and drug resistance of colorectal cancer cells.
We introduced a set of lncRNAs, mRNAs and miRNAs differentially expressed in CRC which might be considered for further experimental research as potential biomarkers of CRC development.
结直肠癌（CRC）是最常见和诊断出的疾病之一。越来越多的证据表明，mRNA 和非编码 RNA 在肿瘤发生中发挥重要的调节作用。识别和确定它们之间的关系有助于癌症的诊断和治疗。
在这里，我们分析了三个微阵列数据集；GSE110715、GSE32323 和 GSE21510，以鉴定 CRC 中差异表达的 lncRNA 和 mRNA。调整后的 p 值≤0.05 被认为具有统计学意义。使用 DAVID 工具进行基因集富集分析。在 miRCancer 数据库中搜索结直肠癌中差异表达的 miRNAs，并使用 miRDB 数据库获得获得的 miRNAs 的靶标。使用 DIANA-LncBase v2 和 RegRNA 2.0 预测 lncRNA-miRNA 相互作用。最后，使用 Cytoscape v3.1 构建 lncRNA-miRNA-mRNA 信号通路网络。
通过分析这三个数据集，总共鉴定出 21 个 mRNA（15 个上调和 6 个下调）和 24 个 lncRNA（18 个上调和 6 个下调）作为 CRC 肿瘤组织和边缘组织之间的共同差异表达基因。然而，构建的 lncRNA-miRNA-mRNA 信号通路网络显示出 6 个 lncRNA（3 个上调和 3 个下调）、7 个 mRNA（2 个上调和 5 个下调）和 6 个 miRNAs（3 个上调和 3 个下调）的收敛。我们发现，lncRNA 如 PCBP1-AS1、UCA1 和 SNHG16 的失调可以隔离一些 miRNAs，如 hsa-miR-582-5p 和 hsa-miR-198，并促进结直肠癌细胞的增殖、侵袭和耐药性。
我们介绍了一组在 CRC 中差异表达的 lncRNA、mRNA 和 miRNAs，它们可能被认为是 CRC 发展的潜在生物标志物，进一步的实验研究。
