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MicroRNAs: a novel promising therapeutic target for cerebral ischemia/reperfusion injury?

Neural Regeneration Research 2015年第11期10卷 1799-1808页

作者： Xiao-li Min Ting-yong Wang Yi Cao Jia Liu Jin-tao Li Ting-hua Wang Institute of Neuroscience Kunming Medical University Faculty of Clinical Medicine Yunnan University of Traditional Chinese Medicine the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine School of Economics of Sichuan University Department of Neurosurgery the Second Affiliated Hospital of Kunming Medical University

To determine the molecular mechanism of cerebral ischemia/reperfusion injury, we examined the micro RNA（mi RNA） expression profile in rat cortex after focal cerebral ischemia/reperfusion injury using mi RNA microarrays and bioinformatic tools to systematically analyze Gene Ontology（GO） function classifications, as well as the signaling pathways of genes targeted by these differentially expressed mi RNAs. Our results show significantly changed mi RNA expression profiles in the reperfusion period after focal cerebral ischemia, with a total of 15 mi RNAs up-regulated and 44 mi RNAs down-regulated. Target genes of these differentially expressed mi RNAs were mainly involved in metabolic and cellular processes, which were identified as hub nodes of a mi RNA-GO-network. The most correlated pathways included D-glutamine and D-glutamate metabolism, the renin-angiotensin system, peroxisomes, the PPAR signaling pathway, SNARE interactions in vesicular transport, and the calcium signaling pathway. Our study suggests that mi RNAs play an important role in the pathological process of cerebral ischemia/reperfusion injury. Understanding mi RNA expression and function may shed light on the molecular mechanism of cerebral ischemia/reperfusion injury.

关键词： nerve regeneration microRNA therapeutic target cerebral ischemia/reperfusion injury miRNA expression profiles bioinformatics analysis Gene Ontology analysis molecular mechanism KEGG pathway neural regeneration

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Cloning and Characterization of miRNAs and Their Targets, Including a Novel miRNA-Targeted NBS-LRR Protein Class Gene in Apple （Golden Delicious）

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Molecular Plant 2014年第1期7卷 218-230页

作者： Chao Ma You Lu Songlin Bai Wennan Zhang Xuwei Duan Dong Meng Zhigang Wang Aide Wang Zongshan Zhou Tianzhong Li Laboratory of Fruit Cell and Molecular Breeding China Agricultural University Beijing 100193 China Research Institute of Pomology Chinese Academy of Agricultural Sciences Xingcheng Liaoning 125100 China College of Horticulture Shenyang Agricultural University Shenyang 110866 China

MicroRNA （miRNA） has emerged as an important regulator of gene expression in plants. 146 miRNAs were identified from apple （Malus domestica cv. Golden Delicious） by bioinformatic analysis and RNA library sequencing. From these, 135 were conserved and 11 were novel miRNAs. Target analysis predicted one of the novel miRNAs, Md-miRLn11 （Malus domestica microRNA Ln11）, targeted an apple nucleotide-binding site （NBS）-Ieucine-rich repeat （LRR） class protein coding gene （Md-NBS）. 5/ RACE assay confirmed the ability of Md-miRLn11 to cleave Md-NBS at the 11-12-nt position. analysis of the expression of Md-miRLn11 and Md-NBS during the optimum invasion period in 40 apple varieties showed that the expression of Md-NBS gene in resistant varieties is higher than in susceptible varieties, with an inverse pattern for Md-miRLn11. Seedlings from the resistant apple variety ＇JiGuan＇ were used to carry out an Agrobacterium infiltration assay, and then inoculated with the apple leaf spot disease. The result showed a clear decline of disease resistance in JiGuan apples. In contrast, the susceptible variety ＇FuJi＇ infiltrated with the Md-NBS gene showed a significant increase in disease resistance. Based on the above results, we propose that Md-miRLn11 regulates Md-NBS gene expression in particular under the condition of pathogen infection, and that the Md-miRLn11 targeting P-loop site may regulate many NBS-LRR protein class genes in woody plants.

关键词： apple microRNA NBS-LRR protein bioinformatics analysis gene function analysis

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Profile of the RNA in exosomes from astrocytes and microglia using deep sequencing:implications for neurodegeneration mechanisms

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Neural Regeneration Research 2022年第3期17卷 608-617页

作者： Hui-Min Xie Xing Su Feng-Yuan Zhang Chao-Lun Dai Rong-Hua Wu Yan Li Xiao-Xiao Han Xing-Mei Feng Bin Yu Shun-Xing Zhu Song-Lin Zhou Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Stomatology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Neurosurgery Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Medical College of Nantong University NantongJiangsu ProvinceChina Laboratory Animals Center Nantong UniversityNantongJiangsu ProvinceChina

Glial cells play an important role in signal transduction,energy metabolism,extracellular ion homeostasis and neuroprotection of the central nervous ***,few studies have explained the potential effects of exosomes from glial cells on central nervous system health and *** this study,the genes expressed in exosomes from astrocytes and microglia were identified by deep RNA *** Encyclopedia of Genes and Genomes analysis indicated that several pathways in these exosomes are responsible for promoting neurodegenerative diseases,including Alzheimer's disease,Parkinson's disease and Huntington's *** ontology analysis showed that extracellular exosome,mitochondrion and growth factor activity were enriched in exosomes from the unique astrocyte group,while extracellular exosome and mitochondrion were enriched in exosomes from the unique microglia ***,combined with the screening of hub genes,the protein-protein interaction network analysis showed that exosomes from astrocytes influence neurodegenerative diseases through metabolic balance and ubiquitin-dependent protein balance,whereas exosomes from microglia influence neurodegenerative diseases through immune inflammation and oxidative *** there were differences in RNA expression between exosomes from astrocytes and microglia,the groups were related by the hub genes,ubiquitin B and heat shock protein family A(Hsp70) member *** B appeared to be involved in pleiotropic regulatory functions,including immune regulation,inflammation inhibition,protein catabolism,intracellular protein transport,exosomes and oxidative *** results revealed the clinical significance of exosomes from glia in neurodegenerative *** study was approved by the Animal Ethics Committee of Nantong University,China(approval No.S20180102-152) on January 2,2018.

关键词： astrocyte bioinformatics analysis central nervous system exosomes microglia neurodegenerative disease RNA transcriptomics UBB

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27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression:A key target potentially linking zearalenone and cancer

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Journal of Pharmaceutical analysis 2024年第3期14卷 371-388页

作者： Haonan Ruan Jing Zhang Yunyun Wang Ying Huang Jiashuo Wu Chunjiao He Tongwei Ke Jiaoyang Luo Meihua Yang Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine Ministry of EducationInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100193China

Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public ***,the mechanisms behind ZEN-induced intestinal immunotoxicity remain *** this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day *** a duration of 14 *** results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the ***,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(Pbioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung *** findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat ***,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.

关键词： Zearalenone Intestinal immunosuppression Apolipoprotein E bioinformatics analysis Cancer

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bioinformatics and in vitro study reveal the roles of microRNA-346 in high glucose-induced human retinal pigment epithelial cell damage

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International Journal of Ophthalmology(English edition) 2023年第11期16卷 1756-1765页

作者： Peng Li Li Wang Qing Liu Zhao-Jiang Du Department of Ophthalmology Xijing 986 Hospital DepartmentFourth Military Medical UniversityXi’an 710054Shaanxi ProvinceChina Ophthalmology Teaching and Research Section of Institute of Medical Technology Xi’an Medical CollegeXi’an 710032Shaanxi ProvinceChina Department of Ophthalmology Xi’an Central HospitalXi’an 710001Shaanxi ProvinceChina

AIM:To study microRNAs(miRNAs)and their potential effects in high glucose-induced human retinal pigment epithelial cell ***:We screened the GSE52233 miRNA expression dataset for differentially expressed miRNAs(DEMs).The target genes of the top 10 DEMs were predicted using miRWalk 2.0 database,followed by function enrichment and protein-protein interaction *** expression was determined in the human retinal pigment epithelial cell line ARPE-19 treated with high glucose(HG)by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).Cell proliferation was determined using cell counting kit(CCK)-8 *** cycle,apoptosis,and reactive oxygen species(ROS)levels were determined by flow *** direct interaction between miRNA and targets was validated using dual-luciferase reporter ***:Thirty-nine DEMs were screened,and we predicted 125 miRNA-mRNA pairs for the top 10 DEMs,including 119 target genes of seven DEMs such as miR-346,which was upregulated in diabetic retinopathy(DR).miR-346 target genes were substantially enriched in the regulation of intracellular transport and retinoic acidinducible gene I(RIG-I)-like receptor signaling *** of three upregulated and downregulated miRNAs were verified by qRT-PCR in HG-treated ARPE-19 *** of miR-346 was elevated in HG treated ARPE-19 cells in a dose-dependent *** inhibited cell proliferation and induced apoptosis,which were partly reversed by transfecting an miR-346 inhibitor,which even decreased the ROS levels elevated due to *** 2(AGO2)was a target of ***:miR-346 is a key miRNA and plays an important role in HG-induced damage in human retinal pigment epithelial cells.

关键词： miRNA miRNA-346 ARPE-19 bioinformatics analysis

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Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on bioinformatics and the Role of NR6A1 in the Progression of HCC

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Journal of Clinical and Translational Hepatology 2022年第5期10卷 901-912页

作者： Zhong-Hua Lin Jie Zhang Li-Kun Zhuang Yong-Ning Xin Shi-Ying Xuan College of Medicine and Pharmaceutics Ocean University of ChinaQingdaoShandongChina Department of Gastroenterology Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Medical College Qingdao UniversityQingdaoShandongChina Clinical Research Center Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina

Background and Aims:Generally acceptable prognostic models for hepatocellular carcinoma(HCC)are not *** study aimed to establish a prognostic model for HCC by identifying immune-related differentially expressed genes(IR-DEGs)and to investigate the potential role of NR6A1 in the progression of ***:bioinformatics analysis using The Cancer Genome Atlas and ImmPort databases was used to identify *** Cox regression and multivariate Cox regression analysis were used to establish a prognostic model of ***-Meier analysis and the receiver operating characteristic(ROC)curves were used to evaluate the performance of the prognostic model,which was further verified in the International Cancer Genome Consortium(ICGC)*** set enrichment analysis was used to explore the potential pathways of *** counting kit 8,colony formation,wound healing,and Transwell migration assays using Huh7 cells,and tumor formation models in nude mice were ***:A prognostic model established based on ten identified IR-DEGs including HSPA4,FABP6,MAPT,NDRG1,APLN,IL17D,LHB,SPP1,GLP1R,and NR6A1,effectively predicted the prognosis of HCC patients,was confirmed by the ROC curves and verified in ICGC ***6A1 expression was significantly up-regulated in HCC patients,and NR6A1 was significantly associated with a low survival *** set enrichment analysis showed the enrichment of cell cycle,mTOR,WNT,and ERBB signaling pathways in patients with high NR6A1 ***6A1 promoted cell proliferation,invasiveness,migration,and malignant tumor formation and growth in vitro and in ***:An effective prognostic model for HCC,based on a novel signature of 10 immune-related genes,was ***6A1 was up-regulated in HCC and was associated with a poor prognosis of ***6A1 promoted cell proliferation,migration,and growth of HCC,most likely through the cell cycle,mTOR,WNT,and ERBB signaling pathways.

关键词： Hepatocellular carcinoma bioinformatics analysis Prognostic model NR6A1 Proliferation Migration Tumorigenesis

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Expression of miR-1304 in patients with esophageal carcinoma and risk factors for recurrence

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World Journal of Gastroenterology 2020年第6期26卷 670-685页

作者： Yun-Gang Luo Li-Wei Duan Xuan Ji Wen-Yuan Jia Yun Liu Mao-Lei Sun Guo-Min Liu Jilin Provincial Medicine Anti-Tumor Engineering Center the Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina Department of Stomatology the Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina Department of Gastroenterology the Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina Department of Orthopedics the Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina

BACKGROUND Esophageal carcinoma is a malignant gastrointestinal tumor with a very poor ***(miR)-1304 is a newly discovered non-coding RNA,which shows differential expression in other cancers,and its clinical value in esophageal carcinoma remains *** To explore the expression of miR-1304 in patients with esophageal carcinoma and its clinical *** The expression of miR-1304 in patients with esophageal carcinoma was analyzed based on the data on miR in esophageal carcinoma downloaded from The Cancer Genome Atlas *** real-time polymerase chain reaction was adopted to determine the expression of miR-1304 in the tissues and serum of *** clinical diagnostic value of miR-1304 and independent factors for recurrence and prognosis of esophageal carcinoma were then *** potential target genes of miR-1304 were predicted,and then analyzed based on gene ontology,Kyoto Encyclopedia of Genes,and Genomes,and protein-protein *** The expression of miR-1304 in the tissues and serum of patients with esophageal carcinoma increased,and was also increased according to the *** with high expression of miR-1304 suffered increased rates of tumor≥3 cm,low differentiation and stage II+***-1304 had a diagnostic value in identifying esophageal carcinoma,tumor size,differentiation and TNM *** size,differentiation,TNM stage,and miR-1304 were independent risk factors for recurrence of esophageal carcinoma,and they had certain predictive and diagnostic value for the recurrence of esophageal ***-eight patients showed a 3-year survival rate of 38.46%,and patients with high expression of miR-1304 had a relatively lower survival *** analysis revealed that tumor size,differentiation,recurrence and miR-1304 were independent factors for the prognosis of ***,miRDB,and Targetscan predicted 20 target genes in *** ontology enrichment analysis found 18 func

关键词： miR-1304 Recurrence Prognosis Diagnosis bioinformatics analysis The Cancer Genome Atlas Esophageal carcinoma

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Lentivirus-mediated short hairpin RNA interference of CENPK inhibits growth of colorectal cancer cells with overexpression of Cullin 4A

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World Journal of Gastroenterology 2022年第37期28卷 5420-5443页

作者： Xian Li Yi-Ru Han Xuefeng Xuefeng Yong-Xiang Ma Guo-Sheng Xing Zhi-Wen Yang Zhen Zhang Lin Shi Xin-Lin Wu Clinical Medical Research Center The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010050Inner Mongolia Autonomous RegionChina Department of Gastrointestinal Surgery The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010050Inner Mongolia Autonomous RegionChina Department of Pathology The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010050Inner Mongolia Autonomous RegionChina

BACKGROUND Colorectal cancer(CRC)is one of the most common malignant tumors *** identification of novel diagnostic and prognostic biomarkers for CRC is a key research *** analysis has revealed high expression of centromere protein K(CENPK)in ***,the role of CENPK in the progression of CRC is not well *** To evaluate the effects of knockdown of CENPK and overexpression of Cullin 4A(CUL4A)in RKO and HCT116 *** Human colon cancer samples were collected and tested using a human gene expression *** identified CENPK as a potential oncogene for CRC based on bioinformatics *** vitro experiments verified the function of this *** investigated the expression of CENPK in RKO and HCT116 cells using quantitative polymerase chain reaction(qPCR),western blot,and flow *** effect of short hairpin RNA(shRNA)virus-infected RKO cells on tumor growth was evaluated in vivo using quantitative analysis of fluorescence *** evaluate the effects of knockdown of CENPK and overexpression of CUL4A in RKO and HCT116 cells,we performed a series of in vitro experiments,using qPCR,western blot,MTT assay,and flow *** We demonstrated overexpression of CENPK in human colon cancer *** was an independent risk factor in patients with *** downstream genes FBX32,CUL4A,and Yesassociated protein isoform 1 were examined to evaluate the regulatory action of CENPK in RKO *** delayed xenograft tumor emergence,slower growth rate,and lower final tumor weight and volume were observed in the CENPK short hairpin RNA virus infected group compared with the CENPK negative control *** CENPK gene interference inhibited the proliferation of RKO cells in vitro and in *** lentivirus-mediated shRNA interference of CENPK inhibited the proliferation of RKO and HCT116 colon cancer cells,with overexpression of the *** We indicated a potential role of CENPK in promo

关键词： Colorectal cancer Centromere protein K bioinformatics analysis Lentivirus-mediated short hairpin RNA interference Cullin 4A

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Identification of differentially expressed genes in ulcerative colitis and verification in a colitis mouse model by bioinformatics analyses

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World Journal of Gastroenterology 2020年第39期26卷 5983-5996页

作者： Lei Shi Xiao Han Jun-Xiang Li Yu-Ting Liao Fu-Shun Kou Zhi-Bin Wang Rui Shi Xing-Jie Zhao Zhong-Mei Sun Yu Hao Department of Immunology and Microbiology School of Life SciencesBeijing University of Chinese MedicineBeijing 100029China Gastroenterology Department Dongfang HospitalBeijing University of Chinese MedicineBeijing 100078China Department of Internal Medicine Beijing Social Welfare HospitalBeijing 100085China

BACKGROUND Ulcerative colitis(UC)is an inflammatory bowel disease that is difficult to diagnose and *** date,the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators,such as C-reactive protein and the erythrocyte sedimentation rate,but these indicators have an unsatisfactory *** this study,we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus(NCBI-GEO)databases and verified the selected core genes in a mouse model of dextran sulfate sodium(DSS)-induced *** To identify UC-related differentially expressed genes(DEGs)using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of *** Two microarray datasets from the NCBI-GEO database were used,and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn *** annotated these genes based on their functions and signaling pathways,and then protein-protein interactions(PPIs)were identified using the Search Tool for the Retrieval of Interacting *** data were further analyzed with Cytoscape software and the Molecular Complex Detection(MCODE)*** core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was ***,colitis model mice were established by administering DSS,and the top three core genes were verified in colitis mice using real-time polymerase chain reaction(PCR).RESULTS One hundred and seventy-seven DEGs,118 upregulated and 59 downregulated,were initially identified from the GEO2R analysis and predominantly participated in inflammation-related *** clusters with close interactions in UC formed:Seventeen core genes were upregulated[C-X-C motif chemokine ligand 13(CXCL13),C-X-C motif chemokine receptor 2(CXCR2),CXCL9,CXCL5,C-C motif chemokine ligand 18,interleukin 1 beta,matrix metallope

关键词： Ulcerative colitis bioinformatics analysis C-X-C motif chemokine ligand 13 Neuropeptide Y receptor Y1 C-X-C motif chemokine receptor 2 Colitis model mice

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Beclin-1/LC3-II dependent macroautophagy was uninfluenced in ischemia-challenged vascular endothelial cells

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Genes & Diseases 2022年第2期9卷 549-561页

作者： Yaping Ma Chaofan Li Yan He Tiwei Fu Li Song Qingsong Ye Fugui Zhang Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing 401147PR China Department of Oral and Maxillofacial Surgery Stomatological Hospital of Chongqing Medical UniversityChongqing 401147PR China Tianyou Hospital Wuhan University of Science&TechnologyWuhanHubei 430064PR China Department of Oral and Maxillofacial Surgery Massachusetts General HospitalBostonMA 02114USA Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education Chongqing 401147PR China Center for Regenerative Medicine Renmin Hospital of Wuhan UniversityWuhanHubei 430060PR China

Autophagy has been extensively studied and occurs in many biological ***,a question remains as to whether ischemia enhances Beclin-1/LC3-II-dependent macroautophagy in vascular endothelial cells,as has been previously ***,the effect of the level of autophagy on cell or skin flap survival still requires *** created a lethal ischemia model in human umbilical vascular endothelial cells(HUVECs),performed quantitative proteomics and bioinformatics analyses,and verified the autophagic status and effect both in vitro and in *** significantly upregulated proteins encoded by autophagy-related genes(ATGs)included ATG2A,ATG3,ATG4B,ATG5,ATG7,ATG9A,ATG12,ATG16,and *** significantly enhanced lysosomal proteins were cathepsin B,cathepsin D,lysosome-associated membrane protein 1(LAMP1),and ***,the differentially expressed proteins excluded Beclin-1,microtubule-associated protein light chain 3(LC3)-I,and *** blot analyses verified that the protein expression levels of Beclin-1,LC3-I,and LC3-II were neither upregulated nor downregulated in ischemia-challenged *** autophagic status was not enhanced by rapamycin in ischemic HUVECs but appeared to be inhibited by *** in vivo study on rats showed that a downregulation in autophagic status jeopardized skin flap *** conclusion,Ischemia neither enhanced nor inhibited Beclin-1/LC3-II-dependent canonical macroautophagy both in vitro and in vivo,in contradiction to previous *** appropriate autophagic homeostasis can minimize cell or skin flap damage.

关键词： Autophagy bioinformatics analysis Human umbilical vein endothelial cell Quantitative proteomics study Skin flap

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