scholarly journals Whole blood transcriptomic investigation identifies long non-coding RNAs as regulators in sepsis

2020 ◽  
Author(s):  
Lixin Cheng ◽  
Chuanchuan Nan ◽  
Lin Kang ◽  
Ning Zhang ◽  
Sheng Liu ◽  
...  

Abstract Background: Sepsis is a fatal disease referring to the presence of a known or strongly suspected infection coupled with systemic and uncontrolled immune activation causing multiple organ failure. However, neither pathogenic long non-coding RNAs (lncRNAs) nor biological network analysis in sepsis draws enough attention to the society of sepsis studies. Methods: We performed an in-silico investigation of the gene coexpression pattern for the patients response to all-cause sepsis in consecutive intensive care unit (ICU) admissions. Sepsis coexpression gene modules were identified using WGCNA and enrichment analysis. lncRNAs were determined as sepsis biomarkers based on the interactions among lncRNAs and the identified modules. Results: Twenty-three sepsis modules, including both differentially expressed modules and prognostic modules, were identified from the whole blood RNA expression profilings of sepsis patients. Five lncRNAs, FENDRR, MALAT1, TUG1, CRNDE, and ANCR, were detected as sepsis regulators based on the interactions among lncRNAs and the identified coexpression modules. Furthermore, we found that CRNDE and MALAT1 may act as miRNA sponges of sepsis related miRNAs to regulate the expression of sepsis modules. Ultimately, FENDRR, MALAT1, TUG1, and CRNDE were reannotated using three independent lncRNA expression datasets and validated as differentially expressed lncRNAs. Conclusion: The procedure facilitates the identification of prognostic biomarkers and novel therapeutic strategies of sepsis. Our findings highlight the importance of transcriptome modularity and regulatory lncRNAs in the progress of sepsis.

2020 ◽  
Author(s):  
Lixin Cheng ◽  
Chuanchuan Nan ◽  
Lin Kang ◽  
Ning Zhang ◽  
Sheng Liu ◽  
...  

Abstract Background: Sepsis is a fatal disease referring to the presence of a known or strongly suspected infection coupled with systemic and uncontrolled immune activation causing multiple organ failure. However, current knowledge of the role of lncRNAs in sepsis is still extremely limited. Methods: We performed an in silico investigation of the gene coexpression pattern for the patients response to all-cause sepsis in consecutive intensive care unit (ICU) admissions. Sepsis coexpression gene modules were identified using WGCNA and enrichment analysis. lncRNAs were determined as sepsis biomarkers based on the interactions among lncRNAs and the identified modules. Results: Twenty-three sepsis modules, including both differentially expressed modules and prognostic modules, were identified from the whole blood RNA expression profiling of sepsis patients. Five lncRNAs, FENDRR, MALAT1, TUG1, CRNDE, and ANCR, were detected as sepsis regulators based on the interactions among lncRNAs and the identified coexpression modules. Furthermore, we found that CRNDE and MALAT1 may act as miRNA sponges of sepsis related miRNAs to regulate the expression of sepsis modules. Ultimately, FENDRR, MALAT1, TUG1, and CRNDE were reannotated using three independent lncRNA expression datasets and validated as differentially expressed lncRNAs. Conclusion: The procedure facilitates the identification of prognostic biomarkers and novel therapeutic strategies of sepsis. Our findings highlight the importance of transcriptome modularity and regulatory lncRNAs in the progress of sepsis.


2020 ◽  
Author(s):  
Xuping Zhu ◽  
Yanyu Li ◽  
Xue Zhu ◽  
Yanmin Jiang ◽  
Xiaowei Zhu ◽  
...  

Abstract Background Long non-coding RNAs (lncRNAs) are important mediators in the pathogenesis of diabetic gastrointestinal autonomic neuropathy, which has just been reported to have a relation to enteric glial cells (EGCs). However, the role of lncRNAs in the pathogenesis of diabetic gastrointestinal autonomic neuropathy, especially EGCs-related gastrointestinal dysfunction, has never been reported. Methods RNA sequencing technology (RNA-Seq) was used to screen the differential lncRNAs and mRNAs in EGCs under hyperglycemia (300 mmol L− 1 high glucose). Results Totally 4678 differentially expressed lncRNAs (DE lncRNAs) and 6244 differentially expressed mRNAs (DE mRNAs) were obtained. GO enrichment analysis and KEGG pathway analysis showed significant differences. 2910 and 1549 co-expressed mRNAs were respectively expressed in up-regulated and down-regulated DE lncRNA target genes. Several up- or down-regulated lncRNAs were at the key junction points of the regulatory network. Protein-protein interaction networks showed highly connected clusters were TP53, AKT1, Casp9, Casp8, Casp3, TNF, etc, which are known closely related to apoptosis. FLRT3, Fras1, and other related target genes, which revealed the potential function of lncRNAs, may be important targets for differential lncRNAs to regulate the apoptosis of glial cells induced by hyperglycemia. Conclusion In this study, the involvement of lncRNAs in EGCs under hyperglycemia was analyzed using transcriptome analysis.


2020 ◽  
Author(s):  
Fuhui Han ◽  
Jing Li ◽  
Nan Liu ◽  
Ranran Zhao ◽  
Lirong Liu ◽  
...  

Abstract Background: Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and its level is affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on lncRNAs involved in sheep intramuscular fat deposition is still in its infancy. Aohan fine-wool sheep (AFWS), China's representative meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of intramuscular fat deposition. We identified lncRNAs by RNA sequencing in sheep longissimus dorsi muscle(LDM) samples at two ages: 2 months (Mth-2) and 12 months (Mth-12).Results: We identified a total of 26,247 genes and 6,935 predicted novel lncRNAs in LDM samples of sheep. Among these, 606 mRNAs and 408 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained targeted genes of differentially expressed lncRNAs and performed an enrichment analysis using Gene Ontology(GO) and the Kyoto Encyclopedia of Genes and Genomes(KEGG). We found these targeted mRNAs were primarily enriched in lipid metabolism, lipid transport, regulation of primary metabolic processes and developmental pathways, such as alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, phosphonate and phosphinate metabolism and cell proliferation. Based on the results of this enrichment analysis, we obtained candidate lncRNAs that potentially regulate lipid deposition and constructed a lncRNA-mRNA co-expression network. We speculated that these lncRNAs have important regulatory roles in intramuscular fat deposition. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of sequencing results by qRT-PCR.Conclusions: Our study provided a list of the lncRNAs and mRNAs related to intramuscular lipid deposition in sheep and lay the foundation for future research on regulatory mechanisms.


Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 201 ◽  
Author(s):  
Hui Ma ◽  
Aixin Ni ◽  
Pingzhuang Ge ◽  
Yunlei Li ◽  
Lei Shi ◽  
...  

Pigeons have the ability to produce milk and feed their squabs. The genetic mechanisms underlying milk production in the crops of ’lactating’ pigeons are not fully understood. In this study, RNA sequencing was employed to profile the transcriptome of lncRNA and mRNA in lactating and non-‘lactating’ pigeon crops. We identified 7066 known and 17,085 novel lncRNAs. Of these lncRNAs, 6166 were differentially expressed. Among the 15,138 mRNAs detected, 6483 were differentially expressed, including many predominant genes with known functions in the milk production of mammals. A GO annotation analysis revealed that these genes were significantly enriched in 55, 65, and 30 pathways of biological processes, cellular components, and molecular functions, respectively. A KEGG pathway enrichment analysis revealed that 12 pathways (involving 544 genes), including the biosynthesis of amino acids, the propanoate metabolism, the carbon metabolism and the cell cycle, were significantly enriched. The results provide fundamental evidence for the better understanding of lncRNAs’ and differentially expressed genes’ (DEGs) regulatory role in the molecular pathways governing milk production in pigeon crops. To our knowledge, this is the first genome-wide investigation of the lncRNAs in pigeon crop associated with milk production. This study provided valuable resources for differentially expressed lncRNAs and mRNAs, improving our understanding of the molecular mechanism of pigeon milk production.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ying Zhang ◽  
Woyu Su ◽  
Bo Zhang ◽  
Yao Ling ◽  
Woo Kyun Kim ◽  
...  

Abstract Background Tibetan chickens, a unique native breed in the Qinghai-Tibet Plateau of China, possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play roles in the hypoxic adaptation of high-altitude animals, although their exact involvement remains unclear. Results This study aimed to elucidate the global landscape of mRNAs, lncRNAs, and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs (ceRNAs) and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos. In total, 354 differentially expressed genes (DE genes), 389 differentially expressed lncRNAs (DE lncRNAs), and 73 differentially expressed miRNAs (DE miRNAs) were identified between Tibetan chickens (TC) and control Chahua chickens (CH). GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis (including blood vessel development and blood circulation) and energy metabolism (including glucose, carbohydrate, and lipid metabolism). The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions, which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens. Conclusions Analysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism. These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.


2018 ◽  
Vol 47 (1) ◽  
pp. 378-389 ◽  
Author(s):  
Xiu-Yan Yang ◽  
Yu-jie Gu ◽  
Tian An ◽  
Jia-Xian Liu ◽  
Yan-Yun Pan ◽  
...  

Background/Aims: The adverse effects of obesity on male fertility have been widely reported. In recent years, the relationship between the differential expression of proteins and long non-coding RNAs with male reproductive disease has been reported. However, the exact mechanism in underlying obesity-induced decreased male fertility remains unclear. Methods: We used isobaric tags for relative and absolute quantification to identify differential protein expression patterns in the testis of rats fed a high-fat diet and normal diet. A microarray-based gene expression analysis protocol was used to compare the differences in long non-coding RNAs in high-fat diet-fed and normal diet-fed rats. Five obviously upregulated or downregulated proteins were examined using western blot to verify the accuracy of their expression. Then, we carried out functional enrichment analysis of the differentially expressed proteins using gene ontology and pathway analysis. Finally, the metabolic Gene Ontology terms and pathways involved in the differential metabolites were analyzed using the MetaboAnalyst 2.0 software to explore the co-expression relationship between long non-coding RNAs and proteins. Results: We found 107 proteins and 263 long non-coding RNAs differentially expressed between rats fed a high-fat diet and normal diet. The Gene Ontology term enrichment analysis showed that the protein function most highly enriched was related to negative regulation of reproductive processes. We also found five Gene Ontology terms and two metabolic pathways upregulated or downregulated for both proteins and long non-coding RNAs. Conclusion: The study revealed different expression levels for both proteins and long non-coding RNAs and showed that the function and metabolic pathways of differently expressed proteins were related to reproductive processes. The Gene Ontology terms and metabolic pathways upregulated or downregulated in both proteins and long non-coding RNAs may provide new candidates to explore the mechanisms of obesity-induced male infertility for both protein and epigenetic pathways.


2020 ◽  
Author(s):  
Shahan Mamoor

Sepsis is a leading cause of mortality (1). We mined published datasets from the whole blood of patients with sepsis to identify differentially expressed genes in the septic state (2, 3). We found changes in RORA expression as among the most significant quantitative differences in sepsis whole blood gene expression. Analysis of a separate dataset (4) demonstrated significant repression of a long non-coding RNA produced at the RORA locus in the blood of patients with sepsis.


2020 ◽  
Vol 11 ◽  
Author(s):  
Xianzuo Zhang ◽  
Kun Chen ◽  
Xiaoxuan Chen ◽  
Nikolaos Kourkoumelis ◽  
Guoyuan Li ◽  
...  

Background: Osteoporosis is a highly heritable skeletal muscle disease. However, the genetic mechanisms mediating the pathogenesis of osteoporosis remain unclear. Accordingly, in this study, we aimed to clarify the transcriptional regulation and heritability underlying the onset of osteoporosis.Methods: Transcriptome gene expression data were obtained from the Gene Expression Omnibus database. Microarray data from peripheral blood monocytes of 73 Caucasian women with high and low bone mineral density (BMD) were analyzed. Differentially expressed messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) were identified. Differences in BMD were then attributed to several gene modules using weighted gene co-expression network analysis (WGCNA). LncRNA/mRNA regulatory networks were constructed based on the WGCNA and subjected to functional enrichment analysis.Results: In total, 3,355 mRNAs and 999 lncRNAs were identified as differentially expressed genes between patients with high and low BMD. The WGCNA yielded three gene modules, including 26 lncRNAs and 55 mRNAs as hub genes in the blue module, 36 lncRNAs and 31 mRNAs as hub genes in the turquoise module, and 56 mRNAs and 30 lncRNAs as hub genes in the brown module. JUN and ACSL5 were subsequently identified in the modular gene network. After functional pathway enrichment, 40 lncRNAs and 16 mRNAs were found to be related to differences in BMD. All three modules were enriched in metabolic pathways. Finally, mRNA/lncRNA/pathway networks were constructed using the identified regulatory networks of lncRNAs/mRNAs and pathway enrichment relationships.Conclusion: The mRNAs and lncRNAs identified in this WGCNA could be novel clinical targets in the diagnosis and management of osteoporosis. Our findings may help elucidate the complex interactions between transcripts and non-coding RNAs and provide novel perspectives on the regulatory mechanisms of osteoporosis.


2021 ◽  
Author(s):  
Ying Zhang ◽  
Woyu Su ◽  
Bo Zhang ◽  
Yao Ling ◽  
Woo Kyun Kim ◽  
...  

Abstract Background: Tibetan chickens, a unique native breed in the Qinghai-Tibet Plateau of China, possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play roles in the hypoxic adaptation of high-altitude animals, although their exact involvement remains unclear.Results: This study aimed to elucidate the global landscape of mRNAs, lncRNAs, and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs (ceRNAs) and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos. In total, 354 differentially expressed genes (DE genes), 389 differentially expressed lncRNAs (DE lncRNAs), and 73 differentially expressed miRNAs (DE miRNAs) were identified between Tibetan chickens (TC) and control Chahua chickens (CH). GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis (including blood vessel development and blood circulation) and energy metabolism (including glucose, carbohydrate, and lipid metabolism). The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions, which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens.Conclusions: Analysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism. These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.


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