A Novel Competing Endogenous RNA Network Associated With the Pathogenesis of Graves’ Ophthalmopathy

Abstract

Background: Growing evidence has recently revealed the characteristics of long noncoding (lncRNA)/circular RNA (circRNA)-microRNA (miRNA)-mRNA networks in numerous human diseases. However, a scientific lncRNA/circRNA-miRNA-mRNA network related to Graves’ ophthalmopathy (GO) remains lacking.Materials and methods: The expression levels of RNAs in GO patients were measured through high-throughput sequencing technology, and the results were proven by quantitative real-time PCR (qPCR). We constructed a protein-protein interaction (PPI) network using the Search Tool for the Retrieval of Interacting Genes (STRING) database and identified hub genes by the Cytoscape plug-in CytoHubba. Then, the miRNAs related to differentially expressed lncRNAs/circRNAs and mRNAs were predicted through seed sequence matching analysis. Correlation coefficient analysis was performed on the interesting RNAs to construct a novel competing endogenous RNA (ceRNA) network.Results: In total, 361 mRNAs, 355 circRNAs, and 242 lncRNAs were differentially expressed in GO patients compared with control patients, 166 pairs were identified, and ceRNA networks were constructed. The qPCR results showed that 4 mRNAs (THBS2, CHRM3, CXCL1, FPR2) and 2 lncRNAs (LINC01820:13, ENST00000499452) were differentially expressed between the GO patients and control patients.Conclusion: An innovative lncRNA/circRNA-miRNA-mRNA ceRNA network between GO patients and control patients was constructed, and two important ceRNA pathways were identified, the LINC01820:13-hsa-miR-27b-3p-FPR2 ceRNA pathway and the ENST00000499452-hsa-miR-27a-3p-CXCL1 pathway, which probably affect the autoimmune response and inflammation in GO patients.

Identification of tRNA-Related Fragments and Their Potential Regulatory Effects in Thyroid-Associated Ophthalmopathy

“…What is certain is that it is a self-reactive lymphocyte-induced autoimmune disease in which immune tolerance is lost, leading to an immune response to TSHR that initiates remodeling of the orbital tissue. Recently, many researchers have tried to further explore TAO pathogenesis by comparing differentially expressed RNAs and proteins between control groups and case groups( Yue et al, 2021 ). In our research, among 50 tRFs found to be dysregulated in the TAO group by RNA sequencing, 2 tRFs (tRF5-GluCTC and tRF5-GluTTC) were upregulated and one (tRF1-ArgTCG) downregulated.…”

Research progress on the pathogenesis of Graves’ ophthalmopathy: Based on immunity, noncoding RNA and exosomes

“…LncRNAs are a type of long-stranded multifunctional RNAs with a length of more than 200 that have been reported to act at many different levels of gene expression, including epigenetic regulation, transcriptional regulation, post-transcriptional regulation, and miRNA regulation (87). Salmena et al suggested the competitive endogenous RNA hypothesis for lncRNA-miRNA interactions (88), which is characterized as mutual interference between coding and non-coding RNAs via miRNA response elements, resulting in an extensive regulatory network in the transcriptome (69).…”

“…The down-regulated of miR-146a levels promotes the development of inflammation, while the up-regulated of its levels allow the remission or termination of the inflammatory response. It has been proposed that miR-155 plays a crucial role in the development of Th17 cells during autoimmunity ( 69 ). Also, miR-155 has an essential role in fibrosis by mediating TGF-1β1 signaling to drive collagen synthesis ( 83 ).…”

“…Salmena et al. suggested the competitive endogenous RNA hypothesis for lncRNA-miRNA interactions ( 88 ), which is characterized as mutual interference between coding and non-coding RNAs via miRNA response elements, resulting in an extensive regulatory network in the transcriptome ( 69 ).…”

“…derived by quantitative real-time PCR that there were differences in the expression of four mRNAs (CHRM3, THBS2, FPR2, CXCL1) and two lncRNAs (LINC01820:13, ENS0000499452) between GO patients and control patients ( 69 ). They hypothesized that LINCO1820:13 up-regulated FPR2 expression by competitively binding to the RNA-induced silencing complex of miR-27b, resulting in autoimmune responses and inflammation in GO patients ( 69 ). ENST0000499452 suppresses miR-27a through the same mechanism, thereby impairing its inhibitory effect on CXCL1 and enhancing immune response, inflammation, and fibrosis in GO patients’ OFs ( 69 ).…”