Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remai...Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.展开更多
Objective:Long noncoding RNAs(lncRNA)play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy.This study aims to identify global research trends and h...Objective:Long noncoding RNAs(lncRNA)play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy.This study aims to identify global research trends and hotspots in the field of lncRNAs in angiogenesis-related diseases and to explore future research directions.Methods:Relevant literature published between 2012 and 2022 was retrieved from the Web of Science Core Collection(WoSCC).A total of 1516 articles on lncRNAs and angiogenesis-related diseases were included for bibliometric analysis.CiteSpace and VOSviewer were used to analyze publication countries,institutions,journals,authors,co cited references,and key words.Results:The number of publications in this field has shown a steadily increasing trend from 2012 to 2022,peaking in 2021.China has the highest number of publications,while the United States ranked highest in centrality.Nanjing Medical University was the most prolific institution.Liu Y was the most productive author,while Wang Y ranked first in co citation frequency.Cell was the most frequently cited journal.The latest terms of burst key words were vascular remodeling,dysfunction,heart,target,suppress,and pulmonary arterial hypertension.Conclusion:From 2012 to 2022,research on lncRNAs in angiogenesis-related diseases has grown significantly.China leads in publication volume,while the United States holds the most academic influence.Emerging research hotspots such as vascular remodeling and dysfunction point to key directions for future research.展开更多
基金supported by the National Natural Science Foundation(82071036,82000973)the Natural Science Foundation of Hunan Province(2022JJ30821,2019JJ50967)the Special Project for the Construction of Innovative Provinces in Hunan Province(2023SK4030),China。
文摘Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.
基金supported by the Natural Science Foundation of Hunan Province,China(2022JJ30869).
文摘Objective:Long noncoding RNAs(lncRNA)play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy.This study aims to identify global research trends and hotspots in the field of lncRNAs in angiogenesis-related diseases and to explore future research directions.Methods:Relevant literature published between 2012 and 2022 was retrieved from the Web of Science Core Collection(WoSCC).A total of 1516 articles on lncRNAs and angiogenesis-related diseases were included for bibliometric analysis.CiteSpace and VOSviewer were used to analyze publication countries,institutions,journals,authors,co cited references,and key words.Results:The number of publications in this field has shown a steadily increasing trend from 2012 to 2022,peaking in 2021.China has the highest number of publications,while the United States ranked highest in centrality.Nanjing Medical University was the most prolific institution.Liu Y was the most productive author,while Wang Y ranked first in co citation frequency.Cell was the most frequently cited journal.The latest terms of burst key words were vascular remodeling,dysfunction,heart,target,suppress,and pulmonary arterial hypertension.Conclusion:From 2012 to 2022,research on lncRNAs in angiogenesis-related diseases has grown significantly.China leads in publication volume,while the United States holds the most academic influence.Emerging research hotspots such as vascular remodeling and dysfunction point to key directions for future research.
