Dataset Information

Characterization of Long Noncoding RNA and mRNA Profiles in Sepsis-Induced Myocardial Depression.

ABSTRACT: Septic shock with heart dysfunction is very common in intensive care units. However, whether long noncoding RNA (lncRNA) and mRNA profiles differ between patients with and without myocardial depression is unknown. We generated rat models of hypodynamic septic shock induced by lipopolysaccharide. A total of 12 rat models was constructed and heart tissue from each was collected. Whole genomic RNA sequencing was performed on left ventricular tissue; 6,508 novel lncRNAs and 432 annotated lncRNAs were identified in heart samples, and 74 lncRNAs were expressed differently in the sepsis and control groups. Gene ontology term enrichment indicated apoptosis and its related pathways showed obvious enrichment, which suggested cell apoptosis could play a critical role in the process of myocardial depression. Furthermore, we focused on one lncRNA from the Pvt1 gene. By silencing this lncRNA, we demonstrated knockdown of Pvt1 expression could induce cell apoptosis in lipopolysaccharide-induced heart cells, through increasing the expression of c-Myc, Bid, Bax, and caspase-3 and decreasing the expression of Myd88 and Bcl-2, thereby proving its functional role in myocardial depression. These results demonstrate that lncRNAs both participate in and mediate the pathological process of myocardial depression. Our study improves the understanding of the basic molecular mechanisms underlying myocardial depression.

SUBMITTER: Zhang TN

PROVIDER: S-EPMC6722300 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Characterization of Long Noncoding RNA and mRNA Profiles in Sepsis-Induced Myocardial Depression.

Zhang Tie-Ning TN Goodwin Julie E JE Liu Bing B Li Da D Wen Ri R Yang Ni N Xia Jing J Zhou Han H Zhang Tao T Song Wen-Liang WL Liu Chun-Feng CF

Molecular therapy. Nucleic acids 20190805

Septic shock with heart dysfunction is very common in intensive care units. However, whether long noncoding RNA (lncRNA) and mRNA profiles differ between patients with and without myocardial depression is unknown. We generated rat models of hypodynamic septic shock induced by lipopolysaccharide. A total of 12 rat models was constructed and heart tissue from each was collected. Whole genomic RNA sequencing was performed on left ventricular tissue; 6,508 novel lncRNAs and 432 annotated lncRNAs wer ...[more]

PMID: 31472370

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Project description:BackgroundConstitution in traditional Chinese medicine (TCM) plays a key role in the genesis, development, and prognosis of diseases. Phlegm-dampness constitution (PDC) is one of the nine constitutions in TCM, susceptible to metabolic disorders, which is mainly manifested by profuse phlegm, loose abdomen, and greasy face. Epidemiologic, genomic, and epigenetic studies have been carried out in previous works, confirming that PDC represents a distinctive population with microcosmic changes related to metabolic disorders. However, whether long noncoding RNAs (lncRNAs) play a regulatory role in metabolic disease in subjects with PDC remains largely unknown. We aimed to investigate distinct lncRNA and mRNA expression signatures and lncRNA-mRNA regulatory networks in the phlegm-dampness constitution (PDC).MethodsThe peripheral blood mononuclear cells (PBMCs) were isolated from the subjects with PDC (n = 13) and balanced constitution (BC) (n = 9). The profiles of lncRNAs and mRNAs in PBMCs were analyzed using microarray and further validated with RT-qPCR. Subsequently, pathway analysis was performed to investigate the function of differentially expressed mRNAs by using Ingenuity Pathway Analysis (IPA).ResultsResults suggested that some mRNAs, which were regulated by the differentially expressed lncRNAs, were mainly enriched in lipid metabolism and immune inflammation-related pathways. This was consistent with the molecular characteristics of previous studies, indicating that the clinical characteristics of metabolic disorders in PDC might be regulated by lncRNAs. Furthermore, by making coexpression network construction as well as cis-regulated target gene analysis, several lncRNA-mRNA pairs with potential regulatory relationships were identified by bioinformatic analyses, including RP11-317J10.2-CA3, RP11-809C18.3-PIP4K2A, LINC0069-RFTN1, TTTY15-ARHGEF9, and AC135048.13-ORAI3.ConclusionsThis study first revealed that the expression characteristics of lncRNAs/mRNAs may be potential biomarkers, indicating that the distinctive physical and clinical characteristics of PDC might be partially attributed to the specific expression signatures of lncRNAs/mRNAs.

Project description:BackgroundLong non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides (nt) that are involved in the pathogenesis and development of various cancers including B cell acute lymphoblastic leukemia (B-ALL). To determine the potential roles of lncRNAs involved in pathogenesis of B-ALL, we analyzed the expression profile of lncRNAs and mRNAs in B-ALL, respectively, and constructed lncRNAs/mRNAs interaction network.MethodsWe performed RNA sequencing of 10 non-leukemic blood disease donors and 10 B-ALL patients for Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Interactions among mRNAs were predicted using the STRING database. Quantitative real time PCR (qRT-PCR) was performed to verify the RNA-seq data of lncRNAs and mRNAs. Potential functions of subtype-specific lncRNAs were determined by using coexpression-based analysis on distally (trans-pattern) located protein-coding genes.ResultsA total of 1813 differentially expressed transcripts (DETs) and 2203 lncRNAs were identified. Moreover, 10 dysregulated lncRNAs and 10 mRNAs were randomly selected, and further assessed by RT-qPCR in vitro. Go and KEGG analysis demonstrated that the differentially expressed mRNAs were most closely associated with myeloid leukocyte activation and in transcriptional misregulation in cancer, respectively. In addition, co-expression analysis demonstrated that these lncRNAs, including MSTRG.27994.3, MSTRG.21740.1, ENST00000456341, MSTRG.14224.1 and MSTRG.20153.1, may mediate the pathogenesis and development of B-ALL via lncRNA-mRNA network interactions.ConclusionsThese results showed that several mRNAs and lncRNAs are aberrantly expressed in the bone marrow of B-ALL patients and play potential roles in B-ALL development, and be useful for diagnostic and/or prognostic purposes in pediatric B-ALL.Data availabilityThe datasets used during our study are available through HARVARD Dataverse Persistent ID doi: https://doi.org/10.7910/DVN/LK9T4Z .

Dataset Information

Characterization of Long Noncoding RNA and mRNA Profiles in Sepsis-Induced Myocardial Depression.

Publications

Characterization of Long Noncoding RNA and mRNA Profiles in Sepsis-Induced Myocardial Depression.

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