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The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

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Neural Regeneration Research 2023年第7期18卷 1591-1600页

作者： Yu-Tian Liu Zhao Xu Wei Liu Sen Ren He-Wei Xiong Tao Jiang Jing Chen Yu Kang Qian-Yun Li Zi-Han Wu Hans-GüNther Machens Xiao-Fan Yang Zhen-Bing Chen Department of Hand Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Geriatrics Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Plastic and Hand Surgery Technical University of MunichMunichGermany

Circular rnas(circrnas)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circrnas.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

关键词： circ_0002538 circRNA sequencing competing endogenous rnas demyelination diabetic peripheral neuropathy miR-138-5 myelination plasmolipin protein profiling Schwann cells

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Bioinformatics Analysis of the Regulatory lncRNA–miRNA–mRNA Network and Drug Prediction in Patients with Pulmonary Arterial Hypertension

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Cardiology Discovery 2023年第2期3卷 85-94页

作者： Xiao Jin Ling Jin Li Han Shiping Zhu Department of Traditional Chinese Medicine The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong 510630China.

Objective:Pulmonary arterial hypertension(PAH)is a cardiovascular disease caused by primary proliferative lesions in pulmonary arterioles.competing endogenous rnas(cernas)have been reported to act as sponges for micrornas(mirnas).To date,however,the mechanisms underlying ceRNA involvement in PAH have not been investigated.This study aimed to construct a PAH-related ceRNA network to further explore the mechanisms of PAH.Methods:A probe reannotation was conducted to identify the long non-coding rnas(lncrnas)and messenger rnas(mrnas)involved in PAH.Based on the reannotation results,the“limma”package was used to identify the differentially expressed genes(DEGs)and lncrnas.The miRcode database was used to predict the lncRNA–miRNA interactions.Then,the mrnas targeted by the mirnas were predicted by using TargetScan,miRTarBase,and miRDB.Based on the above interactions,a ceRNA network was constructed,which was mapped and visualized with Cytoscape 3.6.1 software.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the database.To predict possible drugs or molecules that may mitigate PAH,C-Map analysis was applied to find relevant molecular compounds that can reverse the expression of DEGs in cell lines.Results:The ceRNA network consisted of 174 nodes and 304 links,which included 10 lncrnas,23 mirnas,and 53 mrnas.The hub genes of the ceRNA network for PAH included hsa-miR-17-5p,hsa-miR-20b-5p,MEG3,HCP5,hsa-miR-27a-3p,hsa-miR-107,hsa-miR-142-3p,hsa-miR-363-3p,hsa-miR-301b-3p,and hsa-miR-23b-3p.Calprotectin,irinotecan,and medrysone were found to be the 3 significant compounds.Conclusion:This study found that hsa-miR-17-5p,hsa-miR-20b-5p,MEG3,HCP5,hsa-miR-27a-3p,hsa-miR-107,hsa-miR-142-3p,hsa-miR-363-3p,hsa-miR-301b-3p,and hsa-miR-23b-3p maybe the underlying biomarkers and targets for diagnosis and treatment of PAH.

关键词： Pulmonary arterial hypertension competing endogenous rnas Bioinformatics analysis

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Comprehensive Analysis of Key mrnas and lncrnas in Osteosarcoma Response to Preoperative Chemotherapy with Prognostic Values

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Current Medical Science 2021年第5期41卷 916-929页

作者： Mi LI Wei-ting CHENG Hao LI Zhi ZHANG Xiao-li LU Si-si DENG Jian LI Cai-hong YANG Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Oncology Department Wuhan No.1 Hospital Wuhan 430030China Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Institute of Experimental Immunology University Clinic of Rheinische Friedrich-Wilhelms-UniversityBonn D-53127Germany

Objective:Osteosarcoma is one of the most common types of bone sarcoma with a poor prognosis.However,identifying the predictive factors that contribute to the response to neoadjuvant chemotherapy remains a significant challenge.Methods:A public data series(GSE87437)was downloaded to identify differentially expressed genes(DEGs)and differentially expressed lncrnas(DElncrnas)between osteosarcoma patients that do and do not respond to preoperative chemotherapy.Subsequently,functional analysis of the transcriptome expression profile,regulatory networks of DEGs and DElncrnas,competing endogenous rnas(ceRNA)and protein-protein interaction networks were performed.Furthermore,the function,pathway,and survival analysis of hub genes was performed and drug and disease relationship prediction of DElncRNA was carried out.Results:A total of 626 DEGs,26 DElncrnas,and 18 hub genes were identified.However,only one gene and two lncrnas were found to be suitable as candidate gene and lncrnas respectively.Conclusion:The DEGs,hub genes,candidate gene,and candidate lncrnas screened out in this context were considered as potential biomarkers for the response to neoadjuvant chemotherapy of osteosarcoma.

关键词： osteosarcoma preoperative chemotherapy competing endogenous rnas differentially expressed genes survival analysis

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