Liao Qi, Chen Linbo, Zhang Ning, Xi Yang, Hu Shiyun, Ng Derry Minyao, Ahmed Fatma Yislam Hadi, Zhao Guofang, Fan Xiaoxiang, Xie Yangyang, Dai Xiaoyu, Jin Yanping, Ge Jiaxin, Dong Changzheng, Zhang Xinjun, Guo Junming
Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211 Zhejiang China.
Department of Gastroenterology, The Affiliated People's Hospital of Ningbo University, Ningbo, 315040 Zhejiang China.
Cancer Cell Int. 2020 Sep 7;20:439. doi: 10.1186/s12935-020-01527-x. eCollection 2020.
is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers. functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated by in CRC are currently unknown.
In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets of in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors of were then searched for through bioinformatics analysis. We also constructed a regulatory network for and annotated its functions. Finally, one of the lncRNA targets, , was selected to further explore its expression pattern and functions in CRC.
We were able to identify 19 lncRNA targets of and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factors and as the regulatory co-factors of through bioinformatics analysis. Then, through the analysis of the regulatory network, we found that may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, the up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates that may play a critical part in CRC tumorigenesis and progression. Additionally, expression of was found to be down-regulated in CRC cell lines when expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels of and , further alluding to their regulatory relationship.
In conclusion, the network analysis of targets indicates that may be a significant lncRNA in CRC.
是Kruppel样因子家族的成员，该家族属于参与癌症发生的锌指蛋白亚家族。作为一种转录因子，可调节结直肠癌（CRC）中多种蛋白质编码基因（PCG）。然而，目前尚不清楚CRC中受调控的长链非编码RNA（lncRNA）情况。
在本研究中，我们首先设计了一个计算流程来确定CRC中 的PCG和lncRNA靶点。然后我们分析了lncRNA靶点结合区域的基序模式。通过生物信息学分析寻找 的调控辅助因子。我们还构建了 的调控网络并对其功能进行注释。最后，选择其中一个lncRNA靶点 ，进一步探索其在CRC中的表达模式和功能。
我们能够鉴定出 的19个lncRNA靶点，并发现lncRNA结合位点的基序富含GC。接下来，通过生物信息学分析，我们确定转录因子 和 为 的调控辅助因子。然后，通过对调控网络的分析，我们发现 可能参与DNA复制、DNA修复和细胞周期。此外，在细胞周期模块中， 在CRC细胞系和组织中的上调表达模式得到验证，这与CRC侵袭和远处转移相关。这表明 在CRC肿瘤发生和进展中可能起关键作用。此外，当用siRNA敲低 表达时，发现CRC细胞系中 的表达下调；并且观察到 和 的表达水平之间存在强相关性，进一步暗示了它们之间的调控关系。
总之，对 靶点的网络分析表明 可能是CRC中一种重要的lncRNA。
