Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer
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) regu...
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doaj-3a00fc54b1234b5f9da6580fbcc8b5b12020-11-25T03:36:01ZengBMCCancer Cell International1475-28672020-09-0120111510.1186/s12935-020-01527-xNetwork analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancerQi Liao0Linbo Chen1Ning Zhang2Yang Xi3Shiyun Hu4Derry Minyao Ng5Fatma Yislam Hadi Ahmed6Guofang Zhao7Xiaoxiang Fan8Yangyang Xie9Xiaoyu Dai10Yanping Jin11Jiaxin Ge12Changzheng Dong13Xinjun Zhang14Junming Guo15Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineDepartment of Gastroenterology, The Affiliated People’s Hospital of Ningbo UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineDepartment of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineDepartment of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineDepartment of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineHua Mei Hospital, University of Chinese Academy of ScienceHua Mei Hospital, University of Chinese Academy of ScienceHua Mei Hospital, University of Chinese Academy of ScienceHua Mei Hospital, University of Chinese Academy of ScienceThe Affiliated Hospital of School of Medicine, Ningbo UniversityThe Affiliated Hospital of School of Medicine, Ningbo UniversityDepartment of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineThe Affiliated Hospital of School of Medicine, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineAbstract 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 up-regulating 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.http://link.springer.com/article/10.1186/s12935-020-01527-xLong non-coding RNA (lncRNA)KLF5SNHG12Colorectal cancerBioinformatics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qi Liao Linbo Chen Ning Zhang Yang Xi Shiyun Hu Derry Minyao Ng Fatma Yislam Hadi Ahmed Guofang Zhao Xiaoxiang Fan Yangyang Xie Xiaoyu Dai Yanping Jin Jiaxin Ge Changzheng Dong Xinjun Zhang Junming Guo |
spellingShingle |
Qi Liao Linbo Chen Ning Zhang Yang Xi Shiyun Hu Derry Minyao Ng Fatma Yislam Hadi Ahmed Guofang Zhao Xiaoxiang Fan Yangyang Xie Xiaoyu Dai Yanping Jin Jiaxin Ge Changzheng Dong Xinjun Zhang Junming Guo Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer Cancer Cell International Long non-coding RNA (lncRNA) KLF5 SNHG12 Colorectal cancer Bioinformatics |
author_facet |
Qi Liao Linbo Chen Ning Zhang Yang Xi Shiyun Hu Derry Minyao Ng Fatma Yislam Hadi Ahmed Guofang Zhao Xiaoxiang Fan Yangyang Xie Xiaoyu Dai Yanping Jin Jiaxin Ge Changzheng Dong Xinjun Zhang Junming Guo |
author_sort |
Qi Liao |
title |
Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer |
title_short |
Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer |
title_full |
Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer |
title_fullStr |
Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer |
title_full_unstemmed |
Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer |
title_sort |
network analysis of klf5 targets showing the potential oncogenic role of snhg12 in colorectal cancer |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2020-09-01 |
description |
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 up-regulating 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. |
topic |
Long non-coding RNA (lncRNA) KLF5 SNHG12 Colorectal cancer Bioinformatics |
url |
http://link.springer.com/article/10.1186/s12935-020-01527-x |
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