Dataset Information

Long noncoding RNAs show differential expression profiles and display ceRNA potential in cholesteatoma pathogenesis.

ABSTRACT: Cholesteatoma is a pathologically benign but clinically destructive middle ear disease, which is caused by excessive epidermal migration and uncontrolled hyperproliferation of keratinocytes of squamous epithelium, leading to various clinical manifestations and serious complications, such as hearing loss, dizziness, facial paralysis, meningitis, and hydrocephalus. However, the pathogenesis of cholesteatoma is still not fully understood. Herein, we performed microarray analysis to identify the differentially expressed patterns of lncRNAs in cholesteatoma for the first time. Our data indicated that compared with matched normal skin tissue, lncRNA expression profiles were significantly altered in cholesteatoma. A total of 787 lncRNAs were identified (fold change ?2.0, P<0.05), consisting of 181 upregulated and 606 downregulated lncRNAs. Furthermore, by constructing an lncRNA/miRNA/mRNA competing endogenous RNA (ceRNA) network, we found that lncRNAs, such as lncRNA?uc001kfc.1, had ceRNA potential in cholesteatoma formation. In conclusion, lncRNAs were aberrantly expressed in cholesteatoma compared with normal skin tissues and may play important roles in cholesteatoma formation. Our findings shed novel light on the molecular mechanism of cholesteatoma pathogenesis and suggest that lncRNAs may be potential therapeutic targets for cholesteatoma.

SUBMITTER: Gao J

PROVIDER: S-EPMC5928766 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Long noncoding RNAs show differential expression profiles and display ceRNA potential in cholesteatoma pathogenesis.

Gao Juanjuan J Tang Qi Q Zhu Xiaohui X Wang Shihua S Zhang Yongli Y Liu Wenbin W Gao Zhiqiang Z Yang Hua H

Oncology reports 20180316 5

Cholesteatoma is a pathologically benign but clinically destructive middle ear disease, which is caused by excessive epidermal migration and uncontrolled hyperproliferation of keratinocytes of squamous epithelium, leading to various clinical manifestations and serious complications, such as hearing loss, dizziness, facial paralysis, meningitis, and hydrocephalus. However, the pathogenesis of cholesteatoma is still not fully understood. Herein, we performed microarray analysis to identify the dif ...[more]

PMID: 29565455

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Project description:Autism spectrum disorder (ASD) is a complex disorder of neurodevelopment, the function of long noncoding RNA (lncRNA) in ASD remains essentially unknown. In the present study, gene networks were used to explore the ASD disease mechanisms integrating multiple data types (for example, RNA expression, whole-exome sequencing signals, weighted gene co-expression network analysis, and protein-protein interaction) and datasets (five human postmortem datasets). A total of 388 lncRNAs and five co-expression modules were found to be altered in ASD. The downregulated co-expression M4 module was significantly correlated with ASD, enriched with autism susceptibility genes and synaptic signaling. Integrating lncRNAs from the M4 module and microRNA (miRNA) dysregulation data from the literature identified competing endogenous RNA (ceRNA) network. We identified the downregulated mRNAs that interact with miRNAs by the miRTarBase, miRDB, and TargetScan databases. Our analysis reveals that MIR600HG was downregulated in multiple brain tissue datasets and was closely associated with 9 autism-susceptible miRNAs in the ceRNA network. MIR600HG and target mRNAs (EPHA4, MOAP1, MAP3K9, STXBP1, PRKCE, and SCAMP5) were downregulated in the peripheral blood by quantitative reverse transcription polymerase chain reaction analysis (false discovery rate <0.05). Subsequently, we assessed the role of lncRNA dysregulation in altered mRNA levels. Experimental verification showed that some synapse-associated mRNAs were downregulated after the MIR600HG knockdown. BrainSpan project showed that the expression patterns of MIR600HG (primate-specific lncRNA) and synapse-associated mRNA were similar in different human brain regions and at different stages of development. A combination of support vector machine and random forest machine learning algorithms retrieved the marker gene for ASD in the ceRNA network, and the area under the curve of the diagnostic nomogram was 0.851. In conclusion, dysregulation of MIR600HG, a novel specific lncRNA associated with ASD, is responsible for the ASD-associated miRNA-mRNA axes, thereby potentially regulating synaptogenesis.

Dataset Information

Long noncoding RNAs show differential expression profiles and display ceRNA potential in cholesteatoma pathogenesis.

Publications

Long noncoding RNAs show differential expression profiles and display ceRNA potential in cholesteatoma pathogenesis.

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