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Characterization of dysregulated lncRNA-mRNA network based on ceRNA hypothesis to reveal the occurrence and recurrence of myocardial infarction.

ABSTRACT: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on "ceRNA hypothesis". We systematically integrated lncRNA and mRNA expression profiles and miRNA-target regulatory interactions. The constructed DLMN_MI_OC and DLMN_MI_Re both exhibited biological network characteristics, and functional analysis demonstrated that the networks were specific for MI. Additionally, we identified some lncRNA-mRNA ceRNA modules involved in MI occurrence and recurrence. Finally, two new panel biomarkers defined by four lncRNAs (RP1-239B22.5, AC135048.13, RP11-4O1.2, RP11-285F7.2) from DLMN_MI_OC and three lncRNAs (RP11-363E7.4, CTA-29F11.1, RP5-894A10.6) from DLMN_MI_Re with high classification performance were, respectively, identified in distinguishing controls from patients, and patients with recurrent events from those without recurrent events. This study will provide us new insight into ceRNA-mediated regulatory mechanisms involved in MI occurrence and recurrence, and facilitate the discovery of candidate diagnostic and prognosis biomarkers for MI.

SUBMITTER: Zhang G

PROVIDER: S-EPMC5841419 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Characterization of dysregulated lncRNA-mRNA network based on ceRNA hypothesis to reveal the occurrence and recurrence of myocardial infarction.

Zhang Guangde G Sun Haoran H Zhang Yawei Y Zhao Hengqiang H Fan Wenjing W Li Jianfei J Lv Yingli Y Song Qiong Q Li Jiayao J Zhang Mingyu M Shi Hongbo H

Cell death discovery 20180221

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on "ceRNA hypothesis". We systematic ...[more]

PMID: 29531832

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Project description:Background:Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis and a high incidence. The molecular changes and novel biomarkers of HCC need to be identified to improve the diagnosis and prognosis of this disease. We investigated the current research concentrations of HCC and identified the transcriptomics-related biomarkers of HCC from The Cancer Genome Atlas (TGCA) database. Methods:We investigated the current research concentrations of HCC using literature metrology analysis for studies conducted from 2008 to 2018. We identified long noncoding RNAs (lncRNAs) that correlated with the clinical features and survival prognoses of HCC from The Cancer Genome Atlas (TGCA) database. Differentially expressed genes (lncRNAs, miRNAs, and mRNAs) were also identified by TCGA datasets in HCC tumor tissues. A lncRNA competitive endogenous RNA (ceRNA) network was constructed from lncRNAs based on intersected lncRNAs. Survival times and the association between the expression levels of the key lncRNAs of the ceRNA network and the clinicopathological characteristics of HCC patients were analyzed using TCGA. Real-time polymerase chain reaction (qRT-PCR) was used to validate the reliability of the results in tissue samples from 20 newly-diagnosed HCC patients. Results:Analysis of the literature pertaining to HCC research revealed that current research is focused on lncRNA functions in tumorigenesis and tumor development. A total of 128 HCC dysregulated lncRNAs were identified; 66 were included in the co-expressed ceRNA network. We analyzed survival times and the associations between the expression of 66 key lncRNAs and the clinicopathological features of the HCC patients identified from TCGA. Twenty-six lncRNAs were associated with clinical features of HCC (P < 0.05) and six key lncRNAs were associated with survival time (log-rank test P < 0.05). Six key lncRNAs were selected for the validation of their expression levels in 20 patients with newly diagnosed HCC using qRT-PCR. Consistent fold changes in the trends of up and down regulation between qRT-PCR validation and TCGA proved the reliability of our bioinformatics analysis. Conclusions:We used integrative bioinformatics analysis of the TCGA datasets to improve our understanding of the regulatory mechanisms involved with the functional features of lncRNAs in HCC. The results revealed that lncRNAs are potential diagnostic and prognostic biomarkers of HCC.

Dataset Information

Characterization of dysregulated lncRNA-mRNA network based on ceRNA hypothesis to reveal the occurrence and recurrence of myocardial infarction.

Publications

Characterization of dysregulated lncRNA-mRNA network based on ceRNA hypothesis to reveal the occurrence and recurrence of myocardial infarction.

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