Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer
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PRIMARY RESEARCH
Cancer Cell International Open Access
Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer Qi Liao1† , Linbo Chen4†, Ning Zhang6, Yang Xi3, Shiyun Hu1, Derry Minyao Ng1, Fatma Yislam Hadi Ahmed1, Guofang Zhao5, Xiaoxiang Fan5, Yangyang Xie5, Xiaoyu Dai5, Yanping Jin2, Jiaxin Ge2, Changzheng Dong1, Xinjun Zhang2* and Junming Guo3*
Abstract Background: KLF5 is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers. KLF5 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 KLF5 in CRC are currently unknown. Methods: In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets of KLF5 in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors of KLF5 were then searched for through bioinformatics analysis. We also constructed a regulatory network for KLF5 and annotated its functions. Finally, one of the KLF5 lncRNA targets, SNHG12, was selected to further explore its expression pattern and functions in CRC. Results: We were able to identify 19 lncRNA targets of KLF5 and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factors AR and HSF1 as the regulatory co-factors of KLF5 through bioinformatics analysis. Then, through the analysis of the regulatory network, we found that KLF5 may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, the SNHG12 upregulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates that SNHG12 may play a critical part in CRC tumorigenesis and progression. Additionally, expression of SNHG12 was found to be down-regulated in CRC cell lines when KLF5 expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels of SNHG12 and KLF5, further alluding to their regulatory relationship. Conclusions: In conclusion, the network analysis of KLF5 targets indicates that SNHG12 may be a significant lncRNA in CRC. Keywords: Long non-coding RNA (lncRNA), KLF5, SNHG12, Colorectal cancer, Bioinformatics
*Correspondence: [email protected]; [email protected] † Qi Liao and Linbo Chen contributed equally to this work 2 The Affiliated Hospital of School of Medicine, Ningbo University, Ningbo 315020, China 3 Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, Zhejiang, China Full list of author information is available at the end of the article
Background Colorectal cancer (CRC) is one of the most common cancers in digestive system. CRC is the third most frequent malignancy in males and the second most frequent in females worldwide [1]. Approximately 1.4
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