Zhang Yuwei, Tao Yang, Li Yang, Zhao Jinshun, Zhang Lina, Zhang Xiaohong, Dong Changzheng, Xie Yangyang, Dai Xiaoyu, Zhang Xinjun, Liao Qi
Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang, 315211, China.
Faulty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, Zhejiang, 315211, China.
Funct Integr Genomics. 2018 May;18(3):261-275. doi: 10.1007/s10142-017-0588-2. Epub 2018 Jan 26.
Colorectal cancer (CRC) is among one of the most prevalent and lethiferous diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to function as a key regulatory factor in human cancer, but the potential regulatory mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated several expression profiles to obtain 55 differentially expressed (DE) lncRNAs. We first detected lncRNA interactions with transcription factors, microRNAs, mRNAs, and RNA-binding proteins to construct a regulatory network and then create functional enrichment analyses for them using bioinformatics approaches. We found the upregulated genes in the regulatory network are enriched in cell cycle and DNA damage response, while the downregulated genes are enriched in cell differentiation, cellular response, and cell signaling. We then employed module-based methods to mine several intriguing modules from the overall network, which helps to classify the functions of genes more specifically. Next, we confirmed the validity of our network by comparisons with a randomized network using computational method. Finally, we attempted to annotate lncRNA functions based on the regulatory network, which indicated its potential application. Our study of the lncRNA regulatory network provided significant clues to unveil lncRNAs potential regulatory mechanisms in CRC and laid a foundation for further experimental investigation.
结直肠癌(CRC)是全球最常见且致命的疾病之一。长链非编码RNA(lncRNAs)通常被认为是人类癌症中的关键调节因子,但与CRC相关的lncRNA的潜在调节机制在很大程度上仍不清楚。在这里,我们整合了多个表达谱以获得55个差异表达(DE)lncRNAs。我们首先检测lncRNA与转录因子、微小RNA、mRNA和RNA结合蛋白的相互作用以构建调控网络,然后使用生物信息学方法对它们进行功能富集分析。我们发现调控网络中的上调基因富集于细胞周期和DNA损伤反应,而下调基因则富集于细胞分化、细胞反应和细胞信号传导。然后,我们采用基于模块的方法从整个网络中挖掘出几个有趣的模块,这有助于更具体地分类基因的功能。接下来,我们通过使用计算方法与随机网络进行比较来确认我们网络的有效性。最后,我们尝试基于调控网络注释lncRNA的功能,这表明了其潜在应用。我们对lncRNA调控网络的研究为揭示lncRNA在CRC中的潜在调控机制提供了重要线索,并为进一步的实验研究奠定了基础。