scholarly journals AFCMEasyModel: An Easy Interface for Modeling Competing Endogenous RNA Networks using ODEs

2017 ◽  
Author(s):  
Mohammad M. Tarek

AbstractCompeting endogenous RNA networks have been considered to be important regulators of genetic data expression. Circular RNAs and microRNAs interact to form a circular sponge that have been shown to regulate messenger RNAs and hence regulating gene expression. The kinetics by which these non-coding RNAs interact together affecting gene expression are crucial to understand the mechanism of their regulatory function. Herein, we developed AFCMEasyModel as a user-friendly shiny app that enables users to modify regulation parameters of a competing endogenous RNA network based on interaction between circular RNAs and microRNAs in the simulation environment to form a sponge complex. The App provides the source-code for more customized models and allow users to download simulation plots for supplementation of their publications.The App was made available for public-access at: https://mohammadtarek.shinyapps.io/afcmeasymodel/

Oncogenesis ◽  
2019 ◽  
Vol 8 (11) ◽  
Author(s):  
Wenjie Xia ◽  
Qixing Mao ◽  
Bing Chen ◽  
Lin Wang ◽  
Weidong Ma ◽  
...  

Abstract The proposed competing endogenous RNA (ceRNA) mechanism suggested that diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs could communicate with each other by competing for binding to shared microRNAs. The ceRNA network (ceRNET) is involved in tumor progression and has become a hot research topic in recent years. To date, more attention has been paid to the role of non-coding RNAs in ceRNA crosstalk. However, coding transcripts are more abundant and powerful than non-coding RNAs and make up the majority of miRNA targets. In this study, we constructed a mRNA-mRNA related ceRNET of lung adenocarcinoma (LUAD) and identified the highlighted TWIST1-centered ceRNET, which recruits SLC12A5 and ZFHX4 as its ceRNAs. We found that TWIST1/SLC12A5/ZFHX4 are all upregulated in LUAD and are associated with poorer prognosis. SLC12A5 and ZFHX4 facilitated proliferation, migration, and invasion in vivo and in vitro, and their effects were reversed by miR-194–3p and miR-514a-3p, respectively. We further verified that SLC12A5 and ZFHX4 affected the function of TWIST1 by acting as ceRNAs. In summary, we constructed a mRNA-mRNA related ceRNET for LUAD and highlighted the well-known oncogene TWIST1. Then we verified that SLC12A5 and ZFHX4 exert their oncogenic function by regulating TWIST1 expression through a ceRNA mechanism.


2020 ◽  
Author(s):  
xuanjun liu ◽  
Lan Yan ◽  
Chun Lin ◽  
Yiliang Zhang ◽  
Haofei Miao ◽  
...  

Abstract BackgroundDepression is one of the most common psychiatric disease worldwide. Although the research about the pathogenesis of depression have achieved progress, the detailed effect of non-coding RNAs (ncRNAs) in depression are still not clearly elucidated. This study was aimed to identify non-coding RNA biomarkers in stress-induced depression via comprehensive analysis of competing endogenous RNA networkMethodsIn this present study, we acquired RNA expression from RNA seq expression profile in three mice with depressive-like behaviors using chronic restraint stress paradigm and three C57BL/6J wild-type mice as control mice. ResultsA total of 41 differentially expressed circular RNAs (circRNAs) and 181 differentially expressed messenger RNAs (mRNAs) were up-regulated, and 65 differentially expressed circRNAs and 289 differentially expressed mRNAs were down-regulated, which were selected by a threshold of fold change ≥2 and a p-value < 0.05. Gene Ontology was performed to analyze the biological functions, and we predicted potential signaling pathways based on Kyoto Encyclopedia of Genes and Genomes pathway database. In addition, we constructed a circRNA-microRNA (miRNA)-mRNA regulatory network to further identify non-coding RNAs biomarkers. ConclusionsOur findings provide a promising perspective for further research into molecular mechanisms of depression, and targeting circRNA -mediated competing endogenous RNA (ceRNA) network is a useful strategy to early recognize the depression.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yifang Liao ◽  
Ping Li ◽  
Yanxia Wang ◽  
Hong Chen ◽  
Shangwei Ning ◽  
...  

Abstract Background Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis. Methods Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma. Results This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide). Conclusions The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Huijie Gu ◽  
Xiangyang Cheng ◽  
Jun Xu ◽  
Kaifeng Zhou ◽  
Chong Bian ◽  
...  

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.


2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Klaudia Kulczyńska ◽  
Miroslawa Siatecka

During recent years it has been discovered that long non-coding RNAs are important regulators in many biological processes. In this review, we summarize the role of lncRNA in erythropoiesis. LncRNA are crucial for regulation of gene expression during both proliferation and differentiation stages of red blood cell development. Many are regulated by erythroidspecific transcription factors and some are expressed in a developmental stage-specific manner. The majority of individually studied lncRNAs are involved in regulating the terminal maturation stages of red cell differentiation. Their regulatory function is accomplished by various mechanisms, including direct regulation in cis or trans by the lncRNA product or by the cis-localized presence of the lncRNA transcription itself. These add additional levels of regulation of gene expression during erythropoiesis.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Rituparno Sen ◽  
Suman Ghosal ◽  
Shaoli Das ◽  
Subrata Balti ◽  
Jayprokas Chakrabarti

Competing endogenous RNA, ceRNA, vie with messenger RNAs (mRNAs) for microRNAs (miRNAs) with shared miRNAs responses elements (MREs) and act as modulator of miRNA by influencing the available level of miRNA. It has recently been discovered that, apart from protein-coding ceRNAs, pseudogenes, long noncoding RNAs (lncRNAs), and circular RNAs act as miRNA “sponges” by sharing common MRE, inhibiting normal miRNA targeting activity on mRNA. These MRE sharing elements form the posttranscriptional ceRNA network to regulate mRNA expression. ceRNAs are widely implicated in many biological processes. Recent studies have identified ceRNAs associated with a number of diseases including cancer. This brief review focuses on the molecular mechanism of ceRNA as part of the complex post-transcriptional regulatory circuit in cell and the impact of ceRNAs in development and disease.


Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yucheng Fu ◽  
Qi Liu ◽  
Qiyuan Bao ◽  
Junxiang Wen ◽  
Zhuochao Liu ◽  
...  

Abstract Background Osteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs’ roles in osteosarcoma metastasis are still unknown. Methods Differentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves. Results Five hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcoma patients’ prognosis. Conclusions The current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcoma patients.


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