MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia

MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. The understanding of its gene expression regulation and molecular mechanisms still remains elusive. Started from experimentally verified T-ALL-related miRNAs and genes, we obtained 120 feed-forward loops (FFLs) am...

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Main Authors: Ye, Huashan, Liu, Xiaowen, Lv, Meng, Wu, Yuliang, Kuang, Shuzhen, Gong, Jing, Yuan, Ping, Zhong, Zhaodong, Li, Qiubai, Jia, Haibo, Sun, Jun, Chen, Zhichao, Guo, An-Yuan
Format: Online
Language:English
Published: Oxford University Press 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384304/
id pubmed-3384304
recordtype oai_dc
spelling pubmed-33843042012-06-28 MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia Ye, Huashan Liu, Xiaowen Lv, Meng Wu, Yuliang Kuang, Shuzhen Gong, Jing Yuan, Ping Zhong, Zhaodong Li, Qiubai Jia, Haibo Sun, Jun Chen, Zhichao Guo, An-Yuan Computational Biology T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. The understanding of its gene expression regulation and molecular mechanisms still remains elusive. Started from experimentally verified T-ALL-related miRNAs and genes, we obtained 120 feed-forward loops (FFLs) among T-ALL-related genes, miRNAs and TFs through combining target prediction. Afterwards, a T-ALL miRNA and TF co-regulatory network was constructed, and its significance was tested by statistical methods. Four miRNAs in the miR-17–92 cluster and four important genes (CYLD, HOXA9, BCL2L11 and RUNX1) were found as hubs in the network. Particularly, we found that miR-19 was highly expressed in T-ALL patients and cell lines. Ectopic expression of miR-19 represses CYLD expression, while miR-19 inhibitor treatment induces CYLD protein expression and decreases NF-κB expression in the downstream signaling pathway. Thus, miR-19, CYLD and NF-κB form a regulatory FFL, which provides new clues for sustained activation of NF-κB in T-ALL. Taken together, we provided the first miRNA-TF co-regulatory network in T-ALL and proposed a model to demonstrate the roles of miR-19 and CYLD in the T-cell leukemogenesis. This study may provide potential therapeutic targets for T-ALL and shed light on combining bioinformatics with experiments in the research of complex diseases. Oxford University Press 2012-07 2012-02-23 /pmc/articles/PMC3384304/ /pubmed/22362744 http://dx.doi.org/10.1093/nar/gks175 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ye, Huashan
Liu, Xiaowen
Lv, Meng
Wu, Yuliang
Kuang, Shuzhen
Gong, Jing
Yuan, Ping
Zhong, Zhaodong
Li, Qiubai
Jia, Haibo
Sun, Jun
Chen, Zhichao
Guo, An-Yuan
spellingShingle Ye, Huashan
Liu, Xiaowen
Lv, Meng
Wu, Yuliang
Kuang, Shuzhen
Gong, Jing
Yuan, Ping
Zhong, Zhaodong
Li, Qiubai
Jia, Haibo
Sun, Jun
Chen, Zhichao
Guo, An-Yuan
MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia
author_facet Ye, Huashan
Liu, Xiaowen
Lv, Meng
Wu, Yuliang
Kuang, Shuzhen
Gong, Jing
Yuan, Ping
Zhong, Zhaodong
Li, Qiubai
Jia, Haibo
Sun, Jun
Chen, Zhichao
Guo, An-Yuan
author_sort Ye, Huashan
title MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia
title_short MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia
title_full MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia
title_fullStr MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia
title_full_unstemmed MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia
title_sort microrna and transcription factor co-regulatory network analysis reveals mir-19 inhibits cyld in t-cell acute lymphoblastic leukemia
description T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. The understanding of its gene expression regulation and molecular mechanisms still remains elusive. Started from experimentally verified T-ALL-related miRNAs and genes, we obtained 120 feed-forward loops (FFLs) among T-ALL-related genes, miRNAs and TFs through combining target prediction. Afterwards, a T-ALL miRNA and TF co-regulatory network was constructed, and its significance was tested by statistical methods. Four miRNAs in the miR-17–92 cluster and four important genes (CYLD, HOXA9, BCL2L11 and RUNX1) were found as hubs in the network. Particularly, we found that miR-19 was highly expressed in T-ALL patients and cell lines. Ectopic expression of miR-19 represses CYLD expression, while miR-19 inhibitor treatment induces CYLD protein expression and decreases NF-κB expression in the downstream signaling pathway. Thus, miR-19, CYLD and NF-κB form a regulatory FFL, which provides new clues for sustained activation of NF-κB in T-ALL. Taken together, we provided the first miRNA-TF co-regulatory network in T-ALL and proposed a model to demonstrate the roles of miR-19 and CYLD in the T-cell leukemogenesis. This study may provide potential therapeutic targets for T-ALL and shed light on combining bioinformatics with experiments in the research of complex diseases.
publisher Oxford University Press
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384304/
_version_ 1611539370576183296

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