Abstract:To gain insight into the aetiology of posterior subcapsular congenital cataract from the perspective of transcriptional changes, we conducted an mRNA sequencing analysis of the lenses in posterior subcapsular congenital cataract patients and in normal children. There were 1533 differentially expressed genes from 19,072 genes in the lens epithelial cells of the posterior subcapsular congenital cataract patients compared to in the normal controls at a cut-off criteria of |log2 fold change| of >1 and a p-value… Show more
“…p val < 0.05, including 250 upregulated and 165 downregulated DEGs. 40 R visualized the volcano plot ( Figure 1A ) and heatmap ( Figure 1B ) of the DEGs. Figure 1 Differentially expressed genes identified in the two datasets GSE1919 and GSE77298.…”
Objective
Rheumatoid arthritis (RA) is a nonspecific, chronic, systemic autoimmune disease characterized by symmetric polyarticular synovitis. Bioinformatics analysis of potential biomarkers, mRNA–miRNA–lncRNA axes, and signaling pathways in the pathogenesis of RA provides potential targets and theoretical basis for further research on RA.
Methods
The GSE1919 and GSE77298 datasets were downloaded from the Gene Expression Omnibus database (
http://www.ncbi.nlm.nih.gov/geo
). Perl was used to perform data merging, and R was used to perform batch correction. The “limma” package of R was used to screen differentially expressed genes, and the “clusterProfiler” package was used to perform enrichment analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein–protein interaction network, Cytoscape was used for module analysis, and R was used to screen for hub genes. GraphPad Prism was used to plot the receiver operating characteristic curve of the hub genes. Gene set enrichment analysis and competitive endogenous RNA network analysis were performed on hub genes with the greatest diagnostic values. The hub gene with the greatest diagnostic value was verified using immunohistochemical staining.
Results
We obtained nine hub genes (
ITGB2, VAMP8, HLA-A, PTAFR, SYK, FCER1G, HLA-DPB1, LCP2
, and
ACTR2
) and four mRNA–miRNA–lncRNA axes (ITGB2-hsa-miR-486-3p-SNHG3, ITGB2-hsa-miR-338-5p-XIST, ITGB2-hsa-miR-5581-3p-XIST, and ITGB2-hsa-miR-1226-5p-XIST) related to the pathogenesis of RA. The nine hub genes were highly expressed, and
ITGB2
had the highest diagnostic value for RA. We also identified signaling pathways related to the pathogenesis of RA: Fc epsilon Rl and chemokine signaling pathways. The immunohistochemical results showed that ITGB2 expression was significantly upregulated in RA.
Conclusion
The hub genes, mRNA–miRNA–lncRNA axes, and signaling pathways related to RA pathogenesis identified in this study provide a new research direction for the mechanism, diagnosis, and treatment of RA.
“…p val < 0.05, including 250 upregulated and 165 downregulated DEGs. 40 R visualized the volcano plot ( Figure 1A ) and heatmap ( Figure 1B ) of the DEGs. Figure 1 Differentially expressed genes identified in the two datasets GSE1919 and GSE77298.…”
Objective
Rheumatoid arthritis (RA) is a nonspecific, chronic, systemic autoimmune disease characterized by symmetric polyarticular synovitis. Bioinformatics analysis of potential biomarkers, mRNA–miRNA–lncRNA axes, and signaling pathways in the pathogenesis of RA provides potential targets and theoretical basis for further research on RA.
Methods
The GSE1919 and GSE77298 datasets were downloaded from the Gene Expression Omnibus database (
http://www.ncbi.nlm.nih.gov/geo
). Perl was used to perform data merging, and R was used to perform batch correction. The “limma” package of R was used to screen differentially expressed genes, and the “clusterProfiler” package was used to perform enrichment analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein–protein interaction network, Cytoscape was used for module analysis, and R was used to screen for hub genes. GraphPad Prism was used to plot the receiver operating characteristic curve of the hub genes. Gene set enrichment analysis and competitive endogenous RNA network analysis were performed on hub genes with the greatest diagnostic values. The hub gene with the greatest diagnostic value was verified using immunohistochemical staining.
Results
We obtained nine hub genes (
ITGB2, VAMP8, HLA-A, PTAFR, SYK, FCER1G, HLA-DPB1, LCP2
, and
ACTR2
) and four mRNA–miRNA–lncRNA axes (ITGB2-hsa-miR-486-3p-SNHG3, ITGB2-hsa-miR-338-5p-XIST, ITGB2-hsa-miR-5581-3p-XIST, and ITGB2-hsa-miR-1226-5p-XIST) related to the pathogenesis of RA. The nine hub genes were highly expressed, and
ITGB2
had the highest diagnostic value for RA. We also identified signaling pathways related to the pathogenesis of RA: Fc epsilon Rl and chemokine signaling pathways. The immunohistochemical results showed that ITGB2 expression was significantly upregulated in RA.
Conclusion
The hub genes, mRNA–miRNA–lncRNA axes, and signaling pathways related to RA pathogenesis identified in this study provide a new research direction for the mechanism, diagnosis, and treatment of RA.
“…Recently, COL11A1 has been recruited as novel biomarker and a key player in cancer ( 24 ). COL11A1 is expressed in the mouse lens including the fiber cells ( 25 ) and in the zebrafish model, COL11A1, its knockdown affected lens and optic cup diameter during early development ( 26 ) indicative of a functional role in the lens.…”
Background
Genetically determined cataract is both clinically and molecularly highly heterogeneous. Here, we have identified a heterozygous variant in the lens integral membrane protein LIM2, the second most abundant protein in the lens, responsible for congenital sutural/lamellar cataract in a three-generation Japanese family.
Methods
Whole exome sequencing (WES) was undertaken in one affected and one unaffected individual from a family with autosomal dominant congenital cataract to establish the underlying genetic basis.
Results
A recurrent missense variant LIM2: c.388C>T; p.R130C was identified and found to co-segregate with disease. In addition, one variant COL11A1:c.3788C>T of unknown significance (VUS) was also identified.
Conclusions
We report a variant in LIM2 causing an isolated autosomal-dominant congenital sutural/lamellar cataract in a Japanese family. This is the first report of a LIM2 variant in the Japanese population. Hence, we expand the mutation spectrum of LIM2 variants in different ethnic groups.
“…Therefore, the purpose of this study is to explore the potential mechanism of its occurrence and development. Previously, we performed transcriptome sequencing of capsules from patients with PSC and normal controls and found that HTRA1 was the most significant candidate pathogenic gene in lens epithelial cells [11]. HTRA1 has been previously detected in the lenses of mice [12].…”
Congenital cataract is the leading cause of blindness among children worldwide. Patients with posterior subcapsular congenital cataract (PSC) in the central visual axis can result in worsening vision and stimulus deprivation amblyopia. However, the pathogenesis of PSC remains unclear. This study aims to explore the functional regulation and mechanism of HTRA1 in human lens epithelial cells (HLECs). HTRA1 was significantly downregulated in the lens capsules of children with PSC compared to normal controls. HTRA1 is a suppression factor of transforming growth factor-β (TGF-β) signalling pathway, which plays a key role in cataract formation. The results showed that the TGF-β/Smad signalling pathway was activated in the lens tissue of PSC. The effect of HTRA1 on cell proliferation, migration and apoptosis was measured in HLECs. In primary HLECs, the downregulation of HTRA1 can promote the proliferation and migration of HLECs by activating the TGF-β/Smad signalling pathway and can significantly upregulate the TGF-β/Smad downstream target genes FN1 and α-SMA. HTRA1 was also knocked out in the eyes of C57BL/6J mice via adeno-associated virus-mediated RNA interference. The results showed that HTRA1 knockout can significantly upregulate p-Smad2/3 and activate the TGF-β/Smad signalling pathway, resulting in abnormal proliferation and irregular arrangement of lens epithelial cells and leading to the occurrence of subcapsular cataract. To conclude, HTRA1 was significantly downregulated in children with PSC, and the downregulation of HTRA1 enhanced the proliferation and migration of HLECs by activating the TGF-β/Smad signalling pathway, which led to the occurrence of PSC.
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