Identification of competing endogenous RNA (ceRNA) and micro-RNA profiles and regulatory networks in 4-nonylphenol-induced impairment of sertoli cells
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE167912 | GEO | 2021/06/09
REPOSITORIES: GEO
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Project description:The xenoestrogens nonylphenols (NPs), which are materials used in the plastic polymer industry, are considered endocrine disruptors in a wide range of organisms. Studies have shown that human health problems, such as infertility and reproductive toxicology, are linked with NPs. However, the mechanism by which NPs interfere with male reproduction is not fully elucidated. Here, we found that 4-NP can result in male reproductive impairment and reduce androgen receptor (AR) protein levels in rat sertoli cells in vitro and in vivo. Moreover, we performed RNA sequencing to assess the differential expression of ceRNAs in rat primary sertoli cells treated with 4-NP. Bioinformatics methods, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database and ceRNA functional network analyses, were used to investigate the sequencing data and gain further understanding of the biological processes. Our analysis revealed a core set of mRNAs (Ar, Atf6 and Cbp), and circRNAs (circ673, circ1377, circ1789, and circPTEN) that were selected and validated by RT-qPCR. In addition, the head-to-tail splicing of circ673, circ1377, circ1789, and circPTEN was identified by Sanger sequencing. These findings provide the first insight into the ceRNA expression profiles of rat sertoli cells and reveal that ceRNAs participate in 4-NP-induced impairment of sertoli cell function, thereby indicating potential therapies for both reproductive toxicology and male infertility.
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Project description:Purpose: To uncover the mechanism of 4-nonylphenol-induced impairment of sertoli cells, we used RNA sequencing technology to compare the small RNA expression differences between the control groups and the 4-nonylphenol treated groups. Sertoli cells small RNA profiles of the control groups and the 4-nonylphenol treated groups were generated by deep sequencing, in triplicate. The library quality was determined using a Bioanalyzer 2100 (Agilent). The Illumina BGISEQ platform was used for small RNA sequencing. The quality of RNA-seq reads was examined using FastQC.
2021-06-09 | GSE167909 | GEO
Project description:Purpose: To uncover the mechanism of 4-nonylphenol-induced impairment of sertoli cells, we used RNA sequencing technology to compare the lncRNA expression differences between the control groups and the 4-nonylphenol treated groups. Sertoli cells lncRNA, circRNA, mRNA profiles of the control groups and the 4-nonylphenol treated groups were generated by deep sequencing, in duplicate. The library quality was determined using a Bioanalyzer 2100 (Agilent). The Illumina hiseq X ten platform was used for lnc RNA sequencing. The quality of RNA-seq reads was examined using FastQC.
2021-06-09 | GSE167905 | GEO
Project description:Identification of competing endogenous RNA (ceRNA) and micro-RNA profiles and regulatory networks in 4-nonylphenol-induced impairment of sertoli cells
| PRJNA705486 | ENA
Project description:Identification of competing endogenous RNA (ceRNA) and micro-RNA profiles and regulatory networks in 4-nonylphenol-induced impairment of sertoli cells II
| PRJNA705488 | ENA
Project description:Identification of competing endogenous RNA (ceRNA) and micro-RNA profiles and regulatory networks in 4-nonylphenol-induced impairment of sertoli cells I
| PRJNA705483 | ENA
Project description:Parkinson's disease (PD) is a distinctive clinical syndrome with several causes and clinical manifestations. Aside from an infectious cause, PD is a rapidly developing neurological disorder with a global rise in frequency. Notably, improved knowledge of molecular pathways and the developing novel diagnostic methods may result in better therapy for PD patients. In this regard, the amount of research on ceRNA axes is rising, highlighting the importance of these axes in PD. CeRNAs are transcripts that cross-regulate one another via competition for shared microRNAs (miRNAs). These transcripts may be either coding RNAs (mRNAs) or non-coding RNAs (ncRNAs). This research used a systematic review to assess validated loops of ceRNA in PD. The Prisma guideline was used to conduct this systematic review, which entailed systematically examining the articles of seven databases. Out of 309 entries, forty articles met all criteria for inclusion and were summarized in the appropriate table. CeRNA axes have been described through one of the shared vital components of the axes, including lncRNAs such as NEAT1, SNHG family, HOTAIR, MALAT1, XIST, circRNAs, and lincRNAs. Understanding the multiple aspects of this regulatory structure may aid in elucidating the unknown causal causes of PD and providing innovative molecular therapeutic targets and medical fields.
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Project description:MicroRNAs (miRNAs) are small RNA molecules, about 22 nucleotide long, which post-transcriptionally regulate their target messenger RNAs (mRNAs). They accomplish key roles in gene regulatory networks, ranging from signaling pathways to tissue morphogenesis, and their aberrant behavior is often associated with the development of various diseases. Recently it has been experimentally shown that the way miRNAs interact with their targets can be described in terms of a titration mechanism. From a theoretical point of view titration mechanisms are characterized by threshold effect at near-equimolarity of the different chemical species, hypersensitivity of the system around the threshold, and cross-talk among targets. The latter characteristic has been lately identified as competing endogenous RNA (ceRNA) effect to mark those indirect interactions among targets of a common pool of miRNAs they are in competition for. Here we propose a stochastic model to analyze the equilibrium and out-of-equilibrium properties of a network of [Formula: see text] miRNAs interacting with [Formula: see text] mRNA targets. In particular we are able to describe in detail the peculiar equilibrium and non-equilibrium phenomena that the system displays in proximity to the threshold: (i) maximal cross-talk and correlation between targets, (ii) robustness of ceRNA effect with respect to the model's parameters and in particular to the catalyticity of the miRNA-mRNA interaction, and (iii) anomalous response-time to external perturbations.
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Project description:Coronary heart disease (CHD) is a global health concern, and its molecular origin is not fully elucidated. Dysregulation of ncRNAs has been linked to many metabolic and infectious diseases. This study aimed to explore the role of circRNAs in the pathogenesis of CHD and predicted a candidate circRNA that could be targeted for therapeutic approaches to the disease. circRNAs associated with CHD were identified and CHD gene expression profiles were obtained, and analyzed with GEO2R. In addition, differentially expressed miRNA target genes (miR-DEGs) were identified and subjected to functional enrichment analysis. Networks of circRNA/miRNA/mRNA and the miRNA/affected pathways were constructed. Furthermore, a miRNA/mRNA homology study was performed. We identified that hsa_circ_0126672 was strongly associated with the CHD pathology by competing for endogenous RNA (ceRNA) mechanisms. hsa_circ_0126672 characteristically sponges miR-145-5p, miR-186-5p, miR-548c-3p, miR-7-5p, miR-495-3p, miR-203a-3p, and miR-21. Up-regulation of has_circ_0126672 affected various CHD-related cellular functions, such as atherosclerosis, JAK/STAT, and Apelin signaling pathways. Our results also revealed a perfect and stable interaction for the hybrid of miR-145-5p with NOS1 and RPS6KB1. Finally, miR-145-5p had the highest degree of interaction with the validated small molecules. Henchashsa_circ_0126672 and target miRNAs, notably miR-145-5p, could be good candidates for the diagnosis and therapeutic approaches to CHD.
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Project description:BackgroundWe aimed to construct the lncRNA-associated competing endogenous RNA (ceRNA) network and distinguish feature lncRNAs associated with tendinopathy.MethodsWe downloaded the gene profile of GSE26051 from the Gene Expression Omnibus (GEO), including 23 normal samples and 23 diseased tendons. Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were identified, and functional and pathway enrichment analyses were performed. Protein-protein interaction (PPI) network was constructed and further analyzed by module mining. Moreover, a ceRNA regulatory network was constructed based on the identified lncRNA-mRNA coexpression relationship pairs and miRNA-mRNA regulation pairs.ResultsWe identified 1117 DEmRNAs and 57 DElncRNAs from the GEO data. The downregulated DEmRNAs were particularly associated with muscle contraction and muscle filament, while the upregulated ones were linked to extracellular matrix organization and cell adhesion. From the PPI network, 11 modules were extracted. Genes in MCODE 2 (such as TPM4) were significantly involved in cardiomyopathy, and genes in MCODE 4 (such as COL4A3 and COL4A4) were involved in focal adhesion, ECM-receptor interaction, and PI3K-Akt signaling pathway. The ceRNA network contained 7 lncRNAs (MIR133A1HG, LINC01405, PRKCQ-AS1, C10orf71-AS1, MBNL1-AS1, HOTAIRM1, and DNM3OS), 63 mRNAs, and 41 miRNAs. Downregulated lncRNA MIR133A1HG could competitively bind with hsa-miR-659-3p and hsa-miR-218-1-3p to regulate the TPM3. Meanwhile, MIR133A1HG could competitively bind with hsa-miR-1179 to regulate the COL4A3. Downregulated C10orf71-AS1 could competitively bind with hsa-miR-130a-5p to regulate the COL4A4.ConclusionsSeven important lncRNAs, particularly MIR133A1HG and C10orf71-AS1, were found associated with tendinopathy according to the lncRNA-associated ceRNA network.
| S-EPMC9119753 | biostudies-literature