Expression Signatures of Long Noncoding RNAs in Left Ventricular Noncompaction

Long noncoding RNAs have gained widespread attention in recent years for their crucial role in biological regulation. They have been implicated in a range of developmental processes and diseases including cancer, cardiovascular, and neuronal diseases. However, the role of long noncoding RNAs (lncRNAs) in left ventricular noncompaction (LVNC) has not been explored. In this study, we investigated the expression levels of lncRNAs in the blood of LVNC patients and healthy subjects to identify differentially expressed lncRNA that develop LVNC specific biomarkers and targets for developing therapies using biological pathways. We used Agilent Human lncRNA array that contains both updated lncRNAs and mRNAs probes. We identified 1,568 upregulated and 1,141 downregulated (log fold-change > 2.0) lncRNAs that are differentially expressed between LVNC and the control group. Among them, RP11-1100L3.7 and XLOC_002730 are the most upregulated and downregulated lncRNAs. Using quantitative real-time reverse transcription polymerase chain reaction (RT-QPCR), we confirmed the differential expression of three top upregulated and downregulated lncRNAs along with two other randomly picked lncRNAs. Gene Ontology (GO) and KEGG pathways analysis with these differentially expressed lncRNAs provide insight into the cellular pathway leading to LVNC pathogenesis. We also identified 1,066 upregulated and 1,017 downregulated mRNAs. Gene set enrichment analysis (GSEA) showed that G2M, Estrogen, and inflammatory pathways are enriched in differentially expressed genes (DEG). We also identified miRNA targets for these differentially expressed genes. In this study, we first report the use of LncRNA microarray to understand the pathogenesis of LVNC and to identify several lncRNA and genes and their targets as potential biomarkers.

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Identification of long noncoding RNAs reveals the effects of dinotefuran on the brain in Apis mellifera (Hymenopptera: Apidae)

BMC Genomics ◽

10.1186/s12864-021-07811-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Minjie Huang ◽

Jie Dong ◽

Haikun Guo ◽

Minghui Xiao ◽

Deqian Wang

Keyword(s):

Immune Response ◽

Honey Bee ◽

Honey Bees ◽

Transforming Growth Factor ◽

Sublethal Effects ◽

Inflammatory Responses ◽

Noncoding Rnas ◽

Enrichment Analysis ◽

Long Noncoding Rnas ◽

Gene Set Enrichment Analysis

Abstract Background Dinotefuran (CAS No. 165252–70-0), a neonicotinoid insecticide, has been used to protect various crops against invertebrate pests and has been associated with numerous negative sublethal effects on honey bees. Long noncoding RNAs (lncRNAs) play important roles in mediating various biological and pathological processes, involving transcriptional and gene regulation. The effects of dinotefuran on lncRNA expression and lncRNA function in the honey bee brain are still obscure. Results Through RNA sequencing, a comprehensive analysis of lncRNAs and mRNAs was performed following exposure to 0.01 mg/L dinotefuran for 1, 5, and 10 d. In total, 312 lncRNAs and 1341 mRNAs, 347 lncRNAs and 1458 mRNAs, and 345 lncRNAs and 1155 mRNAs were found to be differentially expressed (DE) on days 1, 5 and 10, respectively. Gene set enrichment analysis (GSEA) indicated that the dinotefuran-treated group showed enrichment in carbohydrate and protein metabolism and immune-inflammatory responses such as glycine, serine and threonine metabolism, pentose and glucuronate interconversion, and Hippo and transforming growth factor-β (TGF-β) signaling pathways. Moreover, the DE lncRNA TCONS_00086519 was shown by fluorescence in situ hybridization (FISH) to be distributed mainly in the cytoplasm, suggesting that it may serve as a competing endogenous RNA and a regulatory factor in the immune response to dinotefuran. Conclusion This study characterized the expression profile of lncRNAs upon exposure to neonicotinoid insecticides in young adult honey bees and provided a framework for further study of the role of lncRNAs in honey bee growth and the immune response.

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Bioinformatics-based Screening of Key Genes for Saponin Metabolism in Quinoa

10.21203/rs.3.rs-139481/v1 ◽

2021 ◽

Author(s):

Chengang Guo ◽

Zhimin wei ◽

Wei Lyu ◽

Yanlou Geng

Keyword(s):

Differentially Expressed Genes ◽

Principal Component ◽

Enrichment Analysis ◽

Hierarchical Cluster ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Differential Analysis ◽

Rna Seq ◽

Protein Coding ◽

Key Genes

Abstract Quinoa saponins have complex, diverse and evident physiologic activities. However, the key regulatory genes for quinoa saponin metabolism are not yet well studied. The purpose of this study was to explore genes closely related to quinoa saponin metabolism. In this study, the significantly differentially expressed genes in yellow quinoa were firstly screened based on RNA-seq technology. Then, the key genes for saponin metabolism were selected by gene set enrichment analysis (GSEA) and principal component analysis (PCA) statistical methods. Finally, the specificity of the key genes was verified by hierarchical clustering. The results of differential analysis showed that 1654 differentially expressed genes were achieved after pseudogenes deletion. Therein, there were 142 long non-coding genes and 1512 protein-coding genes. Based on GSEA analysis, 116 key candidate genes were found to be significantly correlated with quinoa saponin metabolism. Through PCA dimension reduction analysis, 57 key genes were finally obtained. Hierarchical cluster analysis further demonstrated that these key genes can clearly separate the four groups of samples. The present results could provide references for the breeding of sweet quinoa and would be helpful for the rational utilization of quinoa saponins.

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Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.780601 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ya Jun Liu ◽

Alphonse Houssou Hounye ◽

Zheng Wang ◽

Xiaowei Liu ◽

Jun Yi ◽

...

Keyword(s):

Risk Score ◽

Immune Cell ◽

Noncoding Rnas ◽

Enrichment Analysis ◽

Long Noncoding Rnas ◽

Gene Set Enrichment Analysis ◽

Risk Scores ◽

Roc Curve Analysis ◽

Good Reliability ◽

Normal Tissues

Cholangiocarcinoma (CCA) is featured by common occurrence and poor prognosis. Autophagy is a biological process that has been extensively involved in the progression of tumors. Long noncoding RNAs (lncRNAs) have been discovered to be critical in diagnosing and predicting various tumors. It may be valuable to elaborate autophagy-related lncRNAs (ARlncRNAs) in CCA, and indeed, there are still few studies concerning the role of ARlncRNAs in CCA. Here, a prognostic ARlncRNA signature was constructed to predict the survival outcome of CCA patients. Through identification, three differentially expressed ARlncRNAs (DEARlncRNAs), including CHRM3.AS2, MIR205HG, and LINC00661, were screened and were considered predictive signatures. Furthermore, the overall survival (OS) of patients with high-risk scores was significantly lower than that of patients with low scores. Interestingly, the risk score was an independent factor for the OS of patients with CCA. Moreover, receiver operating characteristic (ROC) curve analysis showed that the screened and constructed prognosis signature for 1 year (AUC = 0.884), 3 years (AUC =0.759), and 5 years (AUC = 0.788) presented a high score of accuracy in predicting OS of CCA patients. Gene set enrichment analysis (GSEA) revealed that the three DEARlncRNAs were significantly enriched in CCA-related signaling pathways, including “pathways of basal cell carcinoma”, “glycerolipid metabolism”, etc. Quantitative real-time PCR (qRT-PCR) showed that expressions of CHRM3.AS2, MIR205HG, and LINC00661 were higher in CCA tissues than those in normal tissues, similar to the trends detected in the CCA dataset. Furthermore, Pearson’s analysis reported an intimate correlation of the risk score with immune cell infiltration, indicating a predictive value of the signature for the efficacy of immunotherapy. In addition, the screened lncRNAs were found to have the ability to modulate the expression of mRNAs by interacting with miRNAs based on the established lncRNA-miRNA-mRNA network. In conclusion, our study develops a novel nomogram with good reliability and accuracy to predict the OS of CCA patients, providing a significant guiding value for developing tailored therapy for CCA patients.

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Genomic profiling of cancerous patients identifies FPR2 as an alternative immunotherapeutic target in glioblastoma multiforme

10.1101/2020.12.26.424414 ◽

2020 ◽

Author(s):

Yuqing Yang ◽

Ting Sun ◽

Chuchen Qiu ◽

Dongjing Chen ◽

You Wu

Keyword(s):

Glioblastoma Multiforme ◽

Tumor Progression ◽

Differentially Expressed Genes ◽

Primary Tumor ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Control Group ◽

Western Blots ◽

Potential Biomarker

ABSTRACTBackgroundGlioblastoma multiforme (GBM) is a type of high-grade brain tumor known for its proliferative, invasive property, and low survival rate. Recently, with the advancement in therapeutics for tumors such as targeted therapy, individual cancer-specific biomarkers could be recognized as targets for curative purposes. This study identified six differentially expressed genes that have shown significant implications in clinical field, including FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3. FPR2 was of the same protein family with FPR1, and the latter has been repeatedly reported to promote motility and invasiveness of multiple tumor forms.MethodsThe gene expression profiling of 40 GBM samples and five normal samples from the TCGA database were comprehensively analyzed. The differentially expressed genes (DEGs) were identified using R package and screened by enrichment analysis and examination of protein–protein interaction networks, in order to further explore the functions of DEGs with the highest association with clinical traits and to find hub genes. A qRT-PCR and Western blots were conducted to verify the results of this study.ResultsOur investigation showed that FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly up-regulated in GBM primary tumor compared to the control group. Functional enrichment analysis of the DEGs demonstrated that biological functions related to immune systems, cell division and cell cycle were significantly increased, which were closely related to tumor progression and development. Downstream construction of PPI network analysis indicated that FPR2 was a hub gene involved in high level of interaction with CR3 and VEGFA, which played a key role in inflammatory pathways and cellular dysfunction.ConclusionFPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly over-expressed in primary tumor samples of GBM patients and were involved in cellular functions and pathways contributing to tumor progression. Out of these six pivotal genes, we intensively focused on FPR2, and our analysis and experimental data both suggested its efficacy as a potential biomarker, serving as an alternative immunotherapeutic target for glioblastoma multiforme.

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Identification of Differentially Expressed Genes and Long Noncoding RNAs Associated with Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2019/6078251 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Lu-Mei Chi ◽

Li-Ping Wang ◽

Dan Jiao

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Noncoding Rnas ◽

Gene Expression Omnibus ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Similar Treatment ◽

Blood Samples

Objectives. This study aims to determine differentially expressed genes (DEGs) and long noncoding RNAs (lncRNAs) associated with Parkinson’s disease (PD) using a microarray. Methods. We downloaded the microarray data GSE6613 from the Gene Expression Omnibus, which included 105 samples. We selected 72 samples comprising 22 healthy control blood samples and 50 PD blood samples for further analysis. Later, we used Limma to screen DEGs and differentially expressed lncRNAs (DElncRNAs) and estimated their functions by the Gene Ontology (GO). Besides, the competing endogenous RNA (ceRNA) network, including microRNAs, lncRNAs, and mRNAs, was constructed to elucidate the regulatory mechanism. Furthermore, we performed the KEGG pathway enrichment with mRNAs in the ceRNA regulatory network and constructed a final network, including pathways, mRNAs, microRNAs, and lncRNAs. Results. Overall, we obtained 394 DEGs, including 207 upregulated DEGs and 187 downregulated DEGs, and 7 DElncRNAs, including 2 upregulated DElncRNAs and 5 downregulated DElncRNAs. Insulin-like growth factor-1 receptor (IGF1R) was considerably enriched in the endocytosis pathway. In the ceRNA regulation network, IGF1R was the target of hsa-miR-133b and lncRNAs of XIST, and PART1 could also be the target of hsa-miR-133b. While the upregulated DEGs were enriched in the GO terms of the cytoskeleton, cytoskeletal part, and microtubule cytoskeleton, the downregulated DEGs were enriched in the immune response. PRKACA was markedly enriched in numerous pathways, including the MAPK and insulin signaling pathways. Conclusions. IGF1R, PRKACA, and lncRNA-XIST could be potentially involved in PD, and these diverse molecular mechanisms could support the development of the similar treatment for PD.

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Source of Dietary Fat in Pig Diet Affects Adipose Expression of Genes Related to Cancer, Cardiovascular, and Neurodegenerative Diseases

Genes ◽

10.3390/genes10120948 ◽

2019 ◽

Vol 10 (12) ◽

pp. 948

Author(s):

Maria Oczkowicz ◽

Tomasz Szmatoła ◽

Małgorzata Świątkiewicz

Keyword(s):

Differentially Expressed Genes ◽

Beef Tallow ◽

Rapeseed Oil ◽

Fluid Shear Stress ◽

Coconut Oil ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Coagulation Cascade ◽

P Value

It has been known for many years that excessive consumption of saturated fats has proatherogenic properties, contrary to unsaturated fats. However, the molecular mechanism covering these effects is not fully understood. In this paper, we aimed to identify differentially expressed genes (DEGs) using RNA-sequencing, following feeding pigs with different sources of fat. After comparison of adipose samples from three dietary groups (rapeseed oil (n = 6), beef tallow (n = 5), coconut oil (n = 5)), we identified 29 DEGs (adjusted p-value < 0.05, fold change > 1.3) between beef tallow and rapeseed oil and 2 genes between coconut oil and rapeseed oil groups. No differentially expressed genes were observed between coconut oil and beef tallow groups. Almost all 29 DEGs between rapeseed oil and beef tallow groups are connected to neurodegenerative, cardiovascular diseases, or cancer (e.g., PLAU, CYBB, NCF2, ZNF217, CHAC1, CTCFL). Functional analysis of these genes revealed that they are associated with fluid shear stress response, complement and coagulation cascade, ROS signaling, neurogenesis, and regulation of protein binding and protein catabolic processes. Furthermore, gene set enrichment analysis (GSEA) of the whole datasets from all three comparisons suggests that both beef tallow and coconut oil may trigger changes in the expression level of genes crucial in the pathogenesis of civilization diseases.

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Human 45,X Fibroblast Transcriptome Reveals Distinct Differentially Expressed Genes Including Long Noncoding RNAs Potentially Associated with the Pathophysiology of Turner Syndrome

PLoS ONE ◽

10.1371/journal.pone.0100076 ◽

2014 ◽

Vol 9 (6) ◽

pp. e100076 ◽

Cited By ~ 24

Author(s):

Shriram N. Rajpathak ◽

Shamsudheen Karuthedath Vellarikkal ◽

Ashok Patowary ◽

Vinod Scaria ◽

Sridhar Sivasubbu ◽

...

Keyword(s):

Turner Syndrome ◽

Differentially Expressed Genes ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Differentially Expressed

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Construction of circRNA-miRNA-mRNA Network for Exploring Underlying Mechanisms of Lubrication Disorder

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.580834 ◽

2021 ◽

Vol 9 ◽

Author(s):

Shengnan Cong ◽

Jinlong Li ◽

Jingjing Zhang ◽

Jingyi Feng ◽

Aixia Zhang ◽

...

Keyword(s):

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Control Group ◽

Sodium Reabsorption ◽

Cerna Network ◽

Reporter Assays

Lubrication disorder is a common health issue that manifests as insufficient sexual arousal at the beginning of sex. It often causes physical and psychological distress. However, there are few studies on lubrication disorder, and the complexity of circular RNA (circRNA) and the related competing endogenous RNA (ceRNA) network in lubrication disorder is still poorly known. Therefore, this study aims to build a regulatory circRNA-micro (mi)RNA-mRNA network and explore potential molecular markers of lubrication disorder. In the study, 12 subjects were recruited, including 6 in the lubrication disorder group and 6 in the normal control group. RNA sequencing was exploited to identify the expression profiles of circRNA, miRNA and mRNA between two groups, and then to construct the circRNA-miRNA-mRNA networks. The enrichment analyses of the differentially expressed (DE)-mRNAs were examined via Gene Set Enrichment Analysis (GSEA). Furthermore, the expression level and interactions among circRNA, miRNA, and mRNA were validated using real-time quantitative polymerase chain reaction (RT-qPCR) and dual-luciferase reporter assays. In the results, 73 circRNAs, 287 miRNAs, and 354 target mRNAs were differentially expressed between two groups when taking | Log2 (fold change)| > 1 and P-value < 0.05 as criteria, and then the results of GSEA revealed that DE-mRNAs were linked with “vascular smooth muscle contraction,” “aldosterone regulated sodium reabsorption,” “calcium signaling pathway,” etc. 19 target relationships among 5 circRNAs, 4 miRNAs, and 7 mRNAs were found and constructed the ceRNA network. Among them, hsa-miR-212-5p and hsa-miR-874-3p were demonstrated to be related to the occurrence of lubrication disorder. Eventually, consistent with sequencing, RT-qPCR showed that hsa_circ_0026782 and ASB2 were upregulated while hsa-miR-874-3p was downregulated, and dual-luciferase reporter assays confirmed the interactions among them. In summary, the findings indicate that the circRNA-miRNA-mRNA regulatory network is presented in lubrication disorder, and ulteriorly provide a deeper understanding of the specific regulatory mechanism of lubrication disorder from the perspective of the circRNA-miRNA-mRNA network.

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The Genetics Analysis of Molecular Pathogenesis for Alzheimer's Disease

European Neurology ◽

10.1159/000509799 ◽

2020 ◽

Vol 83 (5) ◽

pp. 458-467

Author(s):

Guanchuan Lin ◽

Kaiyuan Ji ◽

Shiyu Li ◽

Wenli Ma ◽

Xinghua Pan

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Interaction Network ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Brain Regions ◽

Molecular Pathogenesis ◽

Differentially Expressed ◽

Control Group ◽

Membrane Structures

Introduction: The molecular pathogenesis of Alzheimer’s disease (AD) is still not clear, and the relationship between gene expression profile for different brain regions has not been studied. Objective: Bioinformatic analysis at the genetic level has become the best way for the pathogenesis research of AD, which can analyze the abovementioned relationship. Methods: In this study, the datasets of AD were obtained from the Gene Expression Omnibus (GEO), and Qlucore Omics Explorer (QOE) software was used to screen differentially expressed genes of GSE36980 and GSE9770 and verify gene expression of GSE63060. The Gene Ontology (GO) function enrichment analysis of these selected genes was conducted by Database for Annotation, Visualization, and Integrated Discovery (DAVID), and then the gene/protein interaction network was established by STRING to find the related proteins. R language was used for drafting maps and plots. Results: There were 20 differentially expressed genes related to AD selected from GSE36980 (p = 6.2e−6, q = 2.9422e−4) and GSE9770 (p = 3.3e−4, q = 0.016606). Their expression levels of the AD group were lower than those in the control group and varied among different brain regions. Cellular morphogenesis and establishment or maintenance of cell polarity were enriched, and LRRTM1 and RASAL1 were identified by the integration network. Moreover, the analysis of GSE63060 verified the expression level of LRRTM1 and RASAL1 in Alzheimer’s patients, which was much lower than that in normal people aged >65 years. Conclusions: The pathogenesis of AD at molecular levels may link to cell membrane structures and signal transduction; hence, a list of 20 genes, including LRRTM1 and RASAL1,potentially are important for the discovery of treatment target or molecular marker of AD.

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Cardiomyopathy-Associated Gene 1-Sensitive PKC-Dependent Connexin 43 Expression and Phosphorylation in Left Ventricular Noncompaction Cardiomyopathy

Cellular Physiology and Biochemistry ◽

10.1159/000485348 ◽

2017 ◽

Vol 44 (2) ◽

pp. 828-842 ◽

Cited By ~ 7

Author(s):

Yuanyuan Xie ◽

Shenghua Liu ◽

Shengshou Hu ◽

Yingjie Wei

Keyword(s):

Gap Junction ◽

Signaling Pathway ◽

Left Ventricular ◽

Control Group ◽

Myocardial Tissue ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction ◽

Noncompaction Cardiomyopathy ◽

Pkc Signaling ◽

Left Ventricular Noncompaction Cardiomyopathy

Background/Aims: Cardiomyopathy-associated gene 1 (CMYA1) plays an important role in embryonic cardiac development, postnatal cardiac remodeling and myocardial injury repair. Abnormal CMYA1 expression may be involved in cardiac dysplasia and primary cardiomyopathy. Our study aims to establish the relationship between CMYA1 and Left ventricular noncompaction cardiomyopathy (LVNC) pathogenesis. Methods: We explored the effects of CMYA1 on connexins (Cx), which contribute to gap junction intercellular communication (GJIC), and the underlying signaling pathway in human normal tissues, LVNC myocardial tissues and HL1 cells by means of western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, co-immunoprecipitation and scrape loading-dye transfer. Results: CMYA1 expression was inversely associated with Cx43 and Cx40 expression, as determined by gap junction PCR array analysis. An increased expression and disordered distribution of CMYA1 at the intercalated discs in LVNC myocardial tissue was also observed. CMYA1 and Cx43 are co-expressed and interact in myocardial cells. CMYA1 expression was positively correlated with p-Cx43 (S368) via the Protein kinase C (PKC) signaling pathway in myocardial tissue and HL1 cells. The diffusion distance of Lucifer Yellow in the HL1 cells in which CMYA1 was over-expressed or knocked down was significantly less or more than that of the control group, respectively. Conclusion: Abnormal CMYA1 expression affects the expression and phosphorylation of Cx43 through the PKC signaling pathway, which is involved in the regulation of GJIC. CMYA1 participates in the molecular mechanism of LVNC pathogenesis.

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