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Circulating exosomal lncRNA contributes to the pathogenesis of spinal cord injury in rats

Neural Regeneration Research 2023年第4期18卷 889-894页

作者： Jian-An Li Ming-Peng Shi Lin Cong Ming-Yu Gu Yi-Heng Chen Si-Yi Wang Zhen-Hua Li Chun-Fang Zan Wan-Fu Wei Department of Orthopedics Tianjin HospitalTianjinChina School of Clinical Medicine Changchun University of Chinese MedicineChangchunJilin ProvinceChina Department of Orthopedics The Affiliated Hospital of Changchun University of Chinese MedicineChangchunJilin ProvinceChina Division of Vascular Biology I nstitute for Stroke and Dementia Research(ISD)LMU KlinikumLudwig-Maximilians-University(LMU)MunichGermany

Exosome-derived long non-coding RNAs(lncRNAs)are extensively engaged in recovery and repair of the injured spinal cord,through different mechanisms.However,to date no study has systematically evaluated the differentially expressed lncRNAs involved in the development of spinal cord injury.Thus,the aim of this study was to identify key circulating exosome-derived lncRNAs in a rat model of spinal cord injury and investigate their potential actions.To this end,we established a rat model of spinal cord hemisection.Circulating exosomes were extracted from blood samples from spinal cord injury and control(sham)rats and further identified through Western blotting and electron microscopy.RNA was isolated from the exosomes and sequenced.The enrichment analysis demonstrated that there were distinctively different lncRNA and mRNA expression patterns between the two groups.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)functional analysis were performed to determine the possible involvements of upregulated and downregulated lncRNAs in various pathways and different biological processes,as well as their cellular locations and molecular functions.Furthermore,quantitative reverse transcription-polymerase chain reaction showed that the expression of five lncRNAs––ENSRN0T00000067908,XR_590093,XR_591455,XR_360081,and XR_346933––was increased,whereas the expression of XR_351404,XR_591426,XR_353833,XR_590076,and XR_590719 was decreased.Of note,these 10 lncRNAs were at the center of the lncRNA-miRNA-mRNA coexpression network,which also included 198 mRNAs and 41 miRNAs.Taken together,our findings show that several circulating exosomal lncRNAs are differentially expressed after spinal cord injury,suggesting that they may be involved in spinal cord injury pathology and pathogenesis.These lncRNAs could potentially serve as targets for the clinical diagnosis and treatment of spinal cord injury.

关键词： exosome inflammation lncRNA microenvironment miRNA mRNA spinal cord injury spinal cord repair

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Research progress of lncRNA and miRNA in hepatic ischemia-reperfusion injury

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Hepatobiliary & Pancreatic Diseases International 2023年第1期22卷 45-53页

作者： Shan-Fei Zhu Wei Yuan Yong-Liang Du Bai-Lin Wang Department of Hepatobiliary Surgery Guangzhou Red Cross Hospital of Jinan UniversityGuangzhou 510220China

Background:Hepatic ischemia-reperfusion injury(HIRI)is a common complication of liver surgeries,such as hepatectomy and liver transplantation.In recent years,several non-coding RNAs(nc RNAs)including long non-coding RNAs(lnc RNAs)and micro RNAs(mi RNAs)have been identified as factors involved in the pathological progression of HIRI.In this review,we summarized the latest research on lnc RNAs,mi RNAs and the lnc RNA-mi RNA regulatory networks in HIRI.Data sources:The Pub Med and Web of Science databases were searched for articles published up to December 2021 using the following keywords:“hepatic ischemia-reperfusion injury”,“lnc RNA”,“long noncoding RNA”,“mi RNA”and“micro RNA”.The bibliography of the selected articles was manually screened to identify additional studies.Results:The mechanism of HIRI is complex,and involves multiple lnc RNAs and mi RNAs.The roles of lnc RNAs such as AK139328,CCAT1,MALAT1,TUG1 and NEAT1 have been established in HIRI.In addition,numerous mi RNAs are associated with apoptosis,autophagy,oxidative stress and cellular inflammation that accompany HIRI pathogenesis.Based on the literature,we conclude that four lnc RNA-mi RNA regulatory networks mediate the pathological progression of HIRI.Furthermore,the expression levels of some lnc RNAs and mi RNAs undergo significant changes during the progression of HIRI,and thus are potential prognostic markers and therapeutic targets.Conclusions:Complex lnc RNA-mi RNA-m RNA networks regulate HIRI progression through mutual activation and antagonism.It is necessary to screen for more HIRI-associated lnc RNAs and mi RNAs in order to identify novel therapeutic targets.

关键词： ncRNA lncRNA miRNA Hepatic ischemia-reperfusion injury Research progress

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The lncRNA39896–miR166b–HDZs module affects tomato resistance to Phytophthora infestans

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Journal of Integrative Plant Biology 2022年第10期64卷 1979-1993页

作者： Yuhui Hong Yuanyuan Zhang Jun Cui Jun Meng Yinhua Chen Chengwei Zhang Jinxiao Yang Yushi Luan School of Bioengineering Dalian University of TechnologyDalian 116024China State Key Laboratory of Rice Biology China National Rice Research InstituteHangzhou 311400China College of Life Science Hunan Normal UniversityChangsha 410081China School of Computer Science and Technology Dalian University of TechnologyDalian 116024China Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresource College of Tropical CropsHainan UniversityHaikou 570228China Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding Beijing Academy of Agriculture&Forestry SciencesBeijing 100000China

The yield and quality of tomatoes(Solanum lycopersicum)is seriously affected by Phytophthora infestans.The long non-coding RNA(lnc RNA)Sl-lnc RNA39896 is induced after P.infestans infection and was previously predicted to act as an endogenous target mimic(eTM)for the micro RNA Sl-miR166b,which function in stress responses.Here,we further examined the role of Sl-lncRNA39896 and Sl-mi R166b in tomato resistance to P.infestans.Sl-miR166b levels were higher in Sl-lnc RNA39896-knockout mutants than in wild-type plants,and the mutants displayed enhanced resistance to P.infestans.A six-point mutation in the region of Sl-lncRNA39896 that binds to Sl-miR166b disabled the interaction,suggesting that Sl-lnc RNA39896 acts as an e TM for Sl-mi R166b.Overexpressing Sl-miR166b yielded a similar phenotype to that produced by Sl-lncRNA39896-knockout,whereas silencing of Sl-mi R166b impaired resistance.We verified that Sl-miR166b cleaved transcripts of its target classⅢhomeodomain-leucine zipper genes Sl HDZ34and Sl HDZ45.Silencing of Sl HDZ34/45 decreased pathogen accumulation in plants infected with P.infestans.Additionally,jasmonic acid and ethylene contents were elevated following infection in the plants with enhanced resistance.Sl-lnc RNA39896is the first known lnc RNA to negatively regulate resistance to P.infestans in tomato.We propose a novel mechanism in which the lnc RNA39896–mi R166b–HDZ module modulates resistance to P.infestans.

关键词： disease resistance lncRNA miRNA Phytophthora infestans target gene tomato

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M2型巨噬细胞来源的外泌体lncRNA NR_028113.1通过激活JAK2/STAT3通路促进巨噬细胞的极化

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南方医科大学学报 2023年第3期43卷 393-399页

作者：张梦莹李志裴纬亚李雪琴杨辉朱小龙吕坤皖南医学院重大疾病非编码RNA转化研究安徽普通高校重点实验室安徽芜湖241001 皖南医学院弋矶山医院中心实验室安徽芜湖241001 皖南医学院弋矶山医院风湿免疫科安徽芜湖241001

目的探究M2型巨噬细胞来源的外泌体lncRNA NR_028113.1对巨噬细胞极化的影响及机制。方法体外分离并培养BALB/c小鼠骨髓来源的巨噬细胞(BMDMs),IL-4诱导其向M2型巨噬细胞极化后,提取并鉴定M2细胞上清液所分泌的外泌体exosome(M2-exo),qR... 详细信息

目的探究M2型巨噬细胞来源的外泌体lncRNA NR_028113.1对巨噬细胞极化的影响及机制。方法体外分离并培养BALB/c小鼠骨髓来源的巨噬细胞(BMDMs),IL-4诱导其向M2型巨噬细胞极化后,提取并鉴定M2细胞上清液所分泌的外泌体exosome(M2-exo),qRT-PCR检测M2外泌体中lncRNA的表达。将100μg/mL的M2-exo,对照组用等体积的PBS分别与M0巨噬细胞共孵育48 h后,qRT-PCR及Western blot检测各组细胞中Arg1、YM-1、FIZZ1、iNOS和TNF-α的表达,流式细胞术检测CD206^(+)细胞比例,Western blot检测各组细胞JAK2/STAT3蛋白磷酸化水平。设计、合成lncRNA smart silencer特异性抑制lncRNA NR_028113.1的表达,转染M2细胞48 h后提取各组细胞(exo+NC和exo+smart silencer)上清液分泌的外泌体再与M0型巨噬细胞共孵育,检测孵育后各组细胞中Arg1、YM-1、FIZZ1、iNOS和TNF-α的表达以及CD206^(+)细胞比例和JAK2/STAT3信号通路蛋白磷酸化水平。结果lncRNA NR_028113.1在M2型巨噬细胞外泌体中高表达(PlncRNA NR_028113.1的表达后,共培养的M0巨噬细胞中Arg1、YM-1和FIZZ1表达显著下调(PlncRNA NR_028113.1可显著促进巨噬细胞向M2型极化,其机制可能与激活JAK2/STAT3信号通路相关。

关键词：外泌体 lncRNA 巨噬细胞极化 JAK2 STAT3

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The lncRNA MARS modulates the epigenetic reprogramming of the marneral cluster in response to ABA

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Molecular Plant 2022年第5期15卷 840-856页

作者： Thomas Roulé Aurelie Christ Nosheen Hussain Ying Huang Caroline Hartmann Moussa Benhamed Jose Gutierrez-Marcos Federico Ariel Martin Crespi Thomas Blein UniversitéParis-Saclay CNRSINRAEUniversitéEvryInstitute of Plant Sciences Paris-Saclay(IPS2)91190 Gif-sur-YvetteFrance Universitéde Paris Institute of Plant Sciences Paris-Saclay(IPS2)91190 Gif-sur-YvetteFrance Instituto de Agrobiotecnología del Litoral CONICETFBCBUniversidad Nacional del LitoralColectora Ruta Nacional 168 km 03000 Santa FeArgentina School of Life Sciences University of WarwickCoventry CV47ALUK

Clustered organization of biosynthetic non-homologous genes is emerging as a characteristic feature of plant genomes.The co-regulation of clustered genes seems to largely depend on epigenetic reprogram-ming and three-dimensional chromatin conformation.In this study,we identified the long non-coding RNA(lncRNA)MARneral Silencing(MARS),localized inside the Arabidopsis marneral cluster,which con-trols the local epigenetic activation of its surrounding region in response to abscisic acid(ABA).MARS modulates the POLYCOMB REPRESSIVE COMPLEX 1(PRC1)component LIKE HETEROCHROMATIN PROTEIN 1(LHP1)binding throughout the cluster in a dose-dependent manner,determining H3K27me3 deposition and chromatin condensation.In response to ABA,MARS decoys LHP1 away from the cluster and promotes the formation of a chromatin loop bringing together the MARNERAL SYNTHASE 1(MRN1)locus and a distal ABA-responsive enhancer.The enrichment of co-regulated lncRNAs in clustered meta-bolic genes in Arabidopsis suggests that the acquisition of novel non-coding transcriptional units may constitute an additional regulatory layer driving the evolution of biosynthetic pathways.

关键词： lncRNA enhancer cluster chromatin conformation LHP1 ABA seed germination epigenetics marneral

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lncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus

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Zoological Research 2024年第1期45卷 25-35页

作者： Xian-Hui Ning Bing Han Ye Peng Shao-Wu Yin College of Marine Science and Engineering Nanjing Normal UniversityNanjingJiangsu 210023China CAS Key Laboratory of Experimental Marine Biology Center for Ocean Mega-ScienceInstitute of OceanologyChinese Academy of SciencesQingdaoShandong 266071China Co-Innovation Center for Marine Bio-Industry Technology of Jiangsu Province LianyungangJiangsu 222005China

Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)crosstalk.Despite their recognized significance in mammals,research on lncRNAs in lower vertebrates remains limited.In the present study,we characterized the first immune-related lncRNA(pol-lnc78)in the teleost Japanese flounder(Paralichthys olivaceus).Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein(SARM),the fifth discovered member of the Toll/interleukin 1(IL-1)receptor(TIR)adaptor family.This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor(TLR)signaling pathway.Specifically,SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1βand tumor necrosis factor-α(TNF-α).Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3’untranslated region(UTR),thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination.Furthermore,pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression.During infection,the negative regulators pol-lnc78 and SARM were significantly down-regulated,while pol-miR-n199-3p was significantly up-regulated,thus favoring host antibacterial defense.These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.

关键词： lncRNA SARM miRNA ceRNA Antibacterial response

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lncRNA HCG27 Promotes Glucose Uptake Ability of HUVECs by MiR-378a-3p/MAPK1 Pathway

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当代医学科学(英文) 2023年第4期43卷 784-793页

作者： Jing-yi ZHANG Yi JIANG Li-jie WEI Xuan ZHOU Sheng-lan ZHU Hui-ting ZHANG Yu-ting CHEN Peng GAO Jun YU Shao-shuai WANG Ling FENG Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Gestational diabetes mellitus(GDM)is the most common metabolic disorder during pregnancy.lncRNA HLA complex group 27(HCG27)plays a crucial role in various metabolic diseases.However,the relationship between lncRNA HCG27 and GDM is not clear.This study aimed to verify a competing endogenous RNA(ceRNA)interaction regulation axis of miR-378a-3p/mitogen-activated protein kinase 1(MAPK1)regulated by HCG27 in GDM.Methods:lncRNA HCG27 and miR-378a-3p were detected by RT-qPCR.The expression of MAPK1 in umbilical vein endothelial cells(HUVECs)was detected by RT-qPCR and that in the placenta by Western blotting.To explore the relationship among lncRNA HCG27,miR-378a-3p,MAPK1 and the glucose uptake ability of HUVECs,vector HCG27,si-HCG27,miR-378a-3p mimic and inhibitor were transfected to achieve overexpression and inhibition of HCG27 or miR-378a-3p.The interaction between miR-378a-3p and lncRNA HCG27 or MAPK1 was confirmed by the dual-luciferase reporter assay.Besides,glucose consumption by HUVECs was detected by the glucose assay kit.Results:HCG27 expression was significantly decreased in both the placenta and primary umbilical vein endothelial cells,while the expression of miR-378a-3p was significantly increased in GDM tissues,and the expression of MAPK1 was decreased in GDM tissues.This ceRNA interaction regulation axiswas proved to affect the glucose uptake function of HUVECs.The transfection of si-HCG27 could significantly reduce the expression of the MAPK1 protein.If the MAPK1 overexpression plasmid was transfected simultaneously with si-HCG27 transfection,the reduced glucose uptake in HUVECs resulting from the decrease in lncRNA HCG27 was reversed.MiR-378a-3p mimic can significantly reduce the mRNA expression of MAPK1 in HUVECs,whereas miR-378a-3p inhibitor can significantly increase the mRNA expression of MAPK1.The inhibition of miR-378a-3p could restore the decreased glucose uptake of HUVECs treated with si-HCG27.Besides,overexpression of lncRNA HCG27 could restore the glucose uptake ability of the palmi

关键词： lncRNA ceRNA gestational diabetes mellitus human umbilical vein endothelial cells

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Long noncoding RNA(lncRNA)H19:An essential developmental regulator with expanding roles in cancer,stem cell differentiation,and metabolic diseases

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Genes & Diseases 2023年第4期10卷 1351-1366页

作者： Junyi Liao Bowen Chen Zhenglin Zhu Chengcheng Du Shengqiang Gao Guozhi Zhao Piao Zhao Yonghui Wang Annie Wang Zander Schwartz Lily Song Jeffrey Hong William Wagstaff Rex CHaydon Hue HLuu Jiaming Fan Russell RReid Tong-Chuan He Lewis Shi Ning Hu Wei Huang Departments of Orthopedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Orthopedic Research Center Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA The Medical Scientist Training Program The University of Chicago Pritzker School of MedicineChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

关键词： Cancer Epigenetic regulation H19 lncRNA Long-noncoding RNA Metabolic diseases Stem cell differentiation

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lncRNA-AP006284.1 promotes prostate cancer cell growth and motility by forming RNA-DNA triplexes and recruiting GNL3/SFPQ complex to facilitate RASSF7 transcription

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Genes & Diseases 2023年第2期10卷 317-320页

作者： Yali Lu Yan Lin Xiaoyang Zhang Jun Yan Zhe Kong Lu Zhang Chenji Wang Yan Huang Shimin Zhao Yao Li Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringMOE Engineering Research Center of Gene TechnologySchool of Life ScienceFudan UniversityShanghai 200433China Shanghai Engineering Research Center of Industrial Microorganisms School of Life ScienceFudan UniversityShanghai 200433China Institute of Metabolism and Integrative Biology (IMIB) Key Laboratory of Reproduction Regulation of NPFPCFudan UniversityShanghai 200433China Institutes of Biomedical Sciences Fudan UniversityShanghai 200433China Department of Laboratory Animal Science Fudan UniversityShanghai 200032China

Long noncoding RNAs(lncRNAs)are known to be involved in transcriptional regulation and their deregulation is associated with the development of human diseases such as cancer.1,2 lncRNA can directly bind to purine-rich double-stranded DNA sequences through Hoogsteen base pairing to form an RNA-DNA triplex motifs and regulate gene expression.3,4,5 However,its regulatory mechanisms and functions in tumors remain unclear.Here,we report that the LMNTD2 antisense RNA 1(LMNTD2-AS1,also known as AP006284.1)is highly expressed in prostate cancer(PCa)and positively correlated with the expression of its adjacent coding gene N-terminal Ras-association domain family 7(RASSF7).Mechanistically,AP006284.1 tethers to the RASSF7 promoter via RNA-DNA triplexes in cis-acting manner,which enhances chromatin accessibility and recruits the transcription factor complex GNL3/SFPQ to activate the expression of RASSF7,a repressor of the Hippo signaling pathway.Consistently,overexpression of either AP006284.1 or RASSF7 inactivated the Hippo signaling and malignant proliferation of PCa cells.

关键词： expression lncRNA cancer

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四川大学学报（医学版） 2022年第4期53卷 626-636页

作者：顾睿刘敏林苹丰天宇袁航欧德琼李思琦李琴赵岗张洁李凯四川大学华西医院肿瘤中心实验肿瘤研究室成都610041

目的本研究旨在通过挖掘宫颈癌TCGA数据库,分析N6-甲基腺嘌呤(N6-methyladenosine,m^(6)A)修饰相关长链非编码RNA(lncRNA)与宫颈癌预后不良及免疫治疗的相关性,从而有效地评估宫颈癌患者的预后和宫颈癌免疫治疗的可行性。方法基于TCGA... 详细信息

目的本研究旨在通过挖掘宫颈癌TCGA数据库,分析N6-甲基腺嘌呤(N6-methyladenosine,m^(6)A)修饰相关长链非编码RNA(lncRNA)与宫颈癌预后不良及免疫治疗的相关性,从而有效地评估宫颈癌患者的预后和宫颈癌免疫治疗的可行性。方法基于TCGA数据库宫颈癌样本,利用生物信息学的方法鉴定与宫颈癌预后相关的m^(6)A修饰相关lncRNA,并以此构建宫颈癌的预后风险模型。结果从304例患者样本中筛选出343个m^(6)A修饰相关lncRNA,通过单因素Cox回归分析得到26个m^(6)A修饰相关lncRNA与宫颈癌患者预后相关,并利用Lasso回归分析得到7个m^(6)A修饰相关lncRNA(DLEU1、AC099850.4、DDN-AS1、EP300-AS1、AC131159.1、AL441992.2、AL021707.6)用以构建预后风险模型。Kaplan-Meier曲线显示低风险组的OS高于高风险组(PlncRNA表达相关,且在高风险组中表达更高(PlncRNA构建的预后风险模型能够有效预测宫颈癌患者的预后,并能评估以PD1为靶点的免疫治疗疗效。

关键词：宫颈癌 m^(6)A lncRNA 预后免疫治疗

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