LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage

Wei Zhou; Xiaojuan  He; Ziyi Chen; Danping Fan; Yonghua Wang; Hui Feng; Ge  Zhang; Aiping  Lu; Lianbo Xiao

doi:10.1186/s12859-019-2981-4

LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage

Wei Zhou, Xiaojuan He, Ziyi Chen, Danping Fan, Yonghua Wang, Hui Feng, Ge Zhang^*, Aiping Lu^*, Lianbo Xiao^*

^*Corresponding author for this work

Institute of Integrated Bioinformedicine & Translational Science

Research output: Contribution to journal › Journal article › peer-review

19 Citations (Scopus)

Abstract

Background

Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/β-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/β-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases.

Results

A dynamic network of lncRNA HOTAIR-mediated Wnt/β-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation.

Conclusions

Our study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.

Original language	English
Article number	412
Journal	BMC Bioinformatics
Volume	20
DOIs	https://doi.org/10.1186/s12859-019-2981-4
Publication status	Published - Dec 2019

Scopus Subject Areas

Structural Biology
Biochemistry
Molecular Biology
Computer Science Applications
Applied Mathematics

User-Defined Keywords

Cartilage damage
Dynamic mechanism
Dynamic network
LncRNA HOTAIR
Therapeutic targets

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10.1186/s12859-019-2981-4

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title = "LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage",

abstract = "BackgroundCartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/β-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/β-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. ResultsA dynamic network of lncRNA HOTAIR-mediated Wnt/β-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. ConclusionsOur study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.",

keywords = "Cartilage damage, Dynamic mechanism, Dynamic network, LncRNA HOTAIR, Therapeutic targets",

author = "Wei Zhou and Xiaojuan He and Ziyi Chen and Danping Fan and Yonghua Wang and Hui Feng and Ge Zhang and Aiping Lu and Lianbo Xiao",

note = "Funding information: The research is supported by the Hong Kong General Research Fund (HKBU 12122516, HKBU261113, HKBU479111, HKBU478312, HKBU262913), the Natural Science Foundation Council of China (81673773, 81272045, 81470072), the Interdisciplinary Research Matching Scheme (IRMS) of Hong Kong Baptist University (RC-IRMS/12–13/02), the Hong Kong Baptist University Strategic Development Fund (SDF) (SDF13–1209-P01), the Faculty Research Grant of Hong Kong Baptist University (FRG2/14–15/010). The funding bodies did not play any role in the design of the study, collection, analysis, and interpretation of data or writing the manuscript. Publisher copyright: {\textcopyright} The Author(s). 2019",

year = "2019",

month = dec,

doi = "10.1186/s12859-019-2981-4",

language = "English",

volume = "20",

journal = "BMC Bioinformatics",

issn = "1471-2105",

publisher = "BioMed Central Ltd.",

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T1 - LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage

AU - Zhou, Wei

AU - He, Xiaojuan

AU - Chen, Ziyi

AU - Fan, Danping

AU - Wang, Yonghua

AU - Feng, Hui

AU - Zhang, Ge

AU - Lu, Aiping

AU - Xiao, Lianbo

N1 - Funding information: The research is supported by the Hong Kong General Research Fund (HKBU 12122516, HKBU261113, HKBU479111, HKBU478312, HKBU262913), the Natural Science Foundation Council of China (81673773, 81272045, 81470072), the Interdisciplinary Research Matching Scheme (IRMS) of Hong Kong Baptist University (RC-IRMS/12–13/02), the Hong Kong Baptist University Strategic Development Fund (SDF) (SDF13–1209-P01), the Faculty Research Grant of Hong Kong Baptist University (FRG2/14–15/010). The funding bodies did not play any role in the design of the study, collection, analysis, and interpretation of data or writing the manuscript. Publisher copyright: © The Author(s). 2019

PY - 2019/12

Y1 - 2019/12

N2 - BackgroundCartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/β-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/β-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. ResultsA dynamic network of lncRNA HOTAIR-mediated Wnt/β-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. ConclusionsOur study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.

AB - BackgroundCartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/β-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/β-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. ResultsA dynamic network of lncRNA HOTAIR-mediated Wnt/β-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. ConclusionsOur study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.

KW - Cartilage damage

KW - Dynamic mechanism

KW - Dynamic network

KW - LncRNA HOTAIR

KW - Therapeutic targets

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AN - SCOPUS:85070891346

SN - 1471-2105

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JO - BMC Bioinformatics

JF - BMC Bioinformatics

M1 - 412

ER -

LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage

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