Establishment of a Colorectal Cancer-Related MicroRNA-mRNA Regulatory Network by Microarray and Bioinformatics.
Establishment of a Colorectal Cancer-Related MicroRNA-mRNA Regulatory Network by Microarray and Bioinformatics.
复制标题
利用微阵列和生物信息学建立结直肠癌相关MicroRNA-mRNA调控网络
DOI：
10.3389/fgene.2020.560186
复制
发表时间：
2020
影响因子：
3.7
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Jiang D;Xie X;Lu Z;Liu L;Qu Y;Wu S;Li Y;Li G;Wang H;Xu G
结直肠癌（Colorectal cancer，CRC）是世界上发病率和死亡率最高的恶性肿瘤之一。微小RNA（miRNAs）是通过与mRNA结合并调节其表达来影响生物学过程的小的非编码RNA，并且包括miRNA失调的表观遗传改变显著参与CRC的发展。确定miRNA-mRNA网络对CRC的影响可能有助于开发新型治疗靶点和预后生物标志物，甚至提高生存率。本研究应用基因芯片技术筛选大肠癌组织和癌旁正常组织中差异表达的miRNAs（DE miRNAs）和mRNAs（DE mRNAs）。在检测到的基因中，42个miRNAs和142个mRNAs在CRC中显著上调，而23个miRNAs和279个mRNAs显著下调。通过DE miRNAs和反表达DE mRNAs的预测靶点的重叠，建立了DE miRNAs和DE mRNAs在结直肠癌中的网络。此外，DE miRNAs可能靶向的DE mRNAs的蛋白质-蛋白质相互作用网络的形成、功能注释和通路分析、稳定的子网络挖掘以及枢纽基因的确定提供了DE miRNAs和DE mRNAs调节CRC生长的可能机制。最后，对枢纽基因表达和预后潜力的验证为上述结果提供了进一步的支持，并表明CCL-28、GPR 15、PNOC、NUSAP 1及其相互作用的miRNA可能是CRC患者预后的潜在标志。总之，我们成功地建立了基于靶向CRC的微阵列结果的miRNA-mRNA调控网络，这些发现可能阐明用于CRC生长的机制，并确定用于CRC预后和治疗的miRNA相关特征。
Colorectal cancer (CRC) is one of the most malignant cancers with high morbidity and mortality. MicroRNAs (miRNAs) are small non-coding RNAs that affect biological processes by binding to mRNAs and regulating their expression, and epigenetic alterations including miRNA dysregulation are significantly involved in CRC development. Determining the effect of the miRNA-mRNA network on CRC could be helpful for developing novel therapeutic targets and prognostic biomarkers, and even improving survival. In this study, microarray assays were used to screen differentially expressed miRNAs (DE miRNAs) and mRNAs (DE mRNAs) in CRC and the adjacent normal tissues. Among the detected genes, 42 miRNAs and 142 mRNAs were significantly upregulated in CRC, while 23 miRNAs and 279 mRNAs were significantly downregulated. Through overlapping of predicted targets of DE miRNAs and anti-expressed DE mRNAs, networks of DE miRNAs and DE mRNAs in CRC were established. Additionally, the formation of a protein-protein interaction network of DE mRNAs possibly targeted by DE miRNAs, functional annotation and pathway analysis, stable subnetwork mining, and determination of hub genes provided the probable mechanism used by DE miRNAs and DE mRNAs to regulate CRC growth. Finally, validation of expression and prognostic potential of hub genes provided further support for the results above and indicated that CCL-28, GPR15, PNOC, NUSAP1, and their interacted miRNAs may be a potential signature for prognosis of CRC patients. In sum, we successfully established miRNA-mRNA regulatory networks based on microarray results targeting CRC, and these findings may elucidate the mechanisms used for CRC growth and identify miRNA-related signatures for prognosis and treatment of CRC.