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Construction of a long non?coding RNA?mediated transcription factor and gene regulatory triplet network reveals global patterns and biomarkers for ischemic stroke.

ABSTRACT: Ischemic stroke (IS) is a severe neurological disease and a major cause of death and disability throughout the world. A long non?coding (lnc)RNA, transcription factor (TF) and gene can form a lncRNA?mediated regulatory triplet (LncMRT), which is a functional network motif that regulates numerous aspects of human diseases. However, systematic identification and molecular characterization of LncMRTs and their roles in IS has not been carried out. In the present study, a global LncMRT network was constructed and the topological features were characterized based on experimentally verified interactions. An integrated approach was developed to identify significantly dysregulated LncMRTs in peripheral blood mononuclear cells of IS and these dysregulated LncMRT networks exhibited specific topological characteristics and a closer network structure than the global LncMRT network that was constructed. The variation of the risk score for LncMRTs indicated that there were multiple dysregulated patterns of LncMRTs in IS. Numerous core clusters were identified from dysregulated LncMRT networks and these core clusters could distinguish IS patient and matched control samples. Finally, functional analyses demonstrated that LncMRTs associated with IS participated in the regulation of the phosphatidylinositol 3?kinase/protein kinase B signaling pathway. In conclusion, the roles of the LncMRTs in IS were elucidated, which could be beneficial for understanding IS pathogenesis and treatment.

SUBMITTER: Cao Y

PROVIDER: S-EPMC6984793 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Construction of a long non‑coding RNA‑mediated transcription factor and gene regulatory triplet network reveals global patterns and biomarkers for ischemic stroke.

Cao Yuze Y Wang Jianjian J Lu Xiaoyu X Kong Xiaotong X Bo Chunrui C Li Shuang S Li Jie J Sun Xuesong X Wang Na N Tian Kuo K Zhang Huixue H Cui Liying L

International journal of molecular medicine 20191209 2

Ischemic stroke (IS) is a severe neurological disease and a major cause of death and disability throughout the world. A long non‑coding (lnc)RNA, transcription factor (TF) and gene can form a lncRNA‑mediated regulatory triplet (LncMRT), which is a functional network motif that regulates numerous aspects of human diseases. However, systematic identification and molecular characterization of LncMRTs and their roles in IS has not been carried out. In the present study, a global LncMRT network was c ...[more]

PMID: 31894261

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Project description:Background and purposeAccumulating evidence suggests that circular RNAs (circRNAs) are involved in immune and inflammatory processes after acute ischemic stroke (AIS). However, the roles of circRNA-mediated competing endogenous RNA (ceRNA) in modulating immune inflammation of AIS have not yet been determined. This study aimed to construct a circRNA-mediated immune-related ceRNA network and identify novel circRNAs in AIS.MethodsMicroarray data were downloaded from the GEO database and further analysed by R software. Then, we constructed a circRNA-mediated ceRNA network based on interaction information from the bioinformatics database. A topological property analysis of the ceRNA network was conducted to screen novel circRNAs. Finally, we further applied quantitative real-time polymerase chain reaction (qRT-PCR) to two independent sets.ResultsWe constructed an AIS immune-related ceRNA (AISIRC) network containing immune-related genes (IRGs), miRNAs, and circRNAs. Additionally, we extracted the subnetwork from the AISIRC network and screened six immune-related circRNAs. After identification and validation, we finally confirmed that plasma levels of circPTP4A2 and circTLK2 were significantly increased in AIS patients compared with both healthy control subjects (HCs) and transient ischemic attack (TIA) patients. Logistic regression and receiver-operating characteristic (ROC) curve analyses demonstrated that these two circRNAs may function as predictive and discriminative biomarkers for AIS. We also confirmed that plasma levels of circPTP4A2 were elevated in TIA patients compared with HCs and might be an independent risk factor for predicting TIA. Longitudinal analysis of circRNA expression up to 90 days after AIS indicated that the ability of circPTP4A2 and circTLK2 to monitor AIS dynamics was highly desirable.ConclusionIn summary, the circRNA-mediated immune-related ceRNA network was successfully constructed, and two circulating circRNAs (circPTP4A2 and circTLK2) improved sensitivity for the diagnosis of AIS and could be considered diagnostic biomarkers.

Dataset Information

Construction of a long non?coding RNA?mediated transcription factor and gene regulatory triplet network reveals global patterns and biomarkers for ischemic stroke.

Publications

Construction of a long non‑coding RNA‑mediated transcription factor and gene regulatory triplet network reveals global patterns and biomarkers for ischemic stroke.

Similar Datasets

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