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Coronaviruses RNA interacts with host miR-500a-5p and miR-501-5p to regulate multiple pathways

Genes & Diseases 2023年第2期10卷 385-388页

作者： Qi Guo Linghui Tan Jiajia Pan Songfang Wu Jiansong Huang Fang Yu Jinghan Wang Department of Nephrology The First Affiliated HospitalSchool of Medicine Zhejiang UniversityHangzhouZhejiang 310003China Zhejiang University School of Medicine HangzhouZhejiang 310003China Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital Fudan UniversityShanghai 200000China Department of Pathology The First Affiliated HospitalSchool of Medicine Zhejiang UniversityHangzhouZhejiang 310003China Department of Hematology The First Affiliated HospitalSchool of Medicine Zhejiang UniversityHangzhouZhejiang 310003China

The Coronavirus disease is the contagious disease. Clinical manifests vary from no symptoms, upper and lower respiratory tract infections, and even severe acute respiratory distress syndrome and multiple organs failure. Recently, three of new beta-coronaviruses have emerged to cause serious and widespread illness and death, such as the Severe Acute Respiratory Syndrome Coronaviruses (SARS-CoV), Middle East Respiratory Syndrome Coronaviruses (MERS-CoV), and 2019-nCoV (the causative pathogen of Coronavirus Disease 2019 (COVID-19). The COVID-19 is continuing to spread globally. However, the detailed molecular mechanisms have not yet been fully clarified. Since the similarity of the pathological features among 2019-nCoV, SARS-CoV and MERS-CoV, we could speculate the biological features of current COVID-19 by researching those of MERS-CoV and SARS-CoV. Therefore, we analyzed expression levels of miRNA and mRNA profiles of MERS-CoV, SARS-CoV and 2019-nCoV from five public GEO datasets (Table S1). As a result, we found 16 miRNAs potentially target a group of hub genes clustering together to tune the immune response. Notably, viral RNAs have the ability to sponge miR-500a-5p and miR-501-5p, indicating viral RNAs sequestering these two miRNAs to trigger genes expression and contribute to pathogenesis. We hope this study will pave the way to better understand 2019-nCoV pathogenesis and develop the innovative therapeutics.

关键词： miR organs sponge

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miR-126-5p affects the chemosensitivity of colorectal cancer cells by regulating SPRED1, ERK1/2 pathway and apoptosis

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Genes & Diseases 2023年第3期10卷 675-678页

作者： Mingshi Xu Gang Zhang Xiaofan Gu Fangqin Zhao Zhongmin Yang Xiongwen Zhang Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China

Chemoresistance is still one of the main obstacles to treat colorectal cancer(CRC).Substantial studies on biomarkers related to chemoresistance have emerged in recent years.Many microRNAs(miRNA)have been reported to involved in drug resistance and CRC.1 miR-126-5p participates in malignant behaviors of numerous cancers.2,3 However,it is not known if miR-126-5p participates in multidrug resistance in CRC.Especially,the impact of miR-126-5p on drug resistance of CRC and its drug resistance mechanism have not been reported.

关键词： colorectal miR cancer

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The double face of miR-320:cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction

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Signal Transduction and Targeted Therapy 2021年第3期6卷 950-961页

作者： Xudong Zhang Shuai Yuan Huaping Li Jiabing Zhan Feng Wang Jiahui Fan Xiang Nie Yan Wang Zheng Wen Yanghui Chen Chen Chen Dao Wen Wang Division of Cardiology Tongji HospitalTongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic DisordersHuazhong University of Science and TechnologyWuhan 430030China

MicroRNAs(miRNAs)are aberrantly expressed in the pathophysiologic process of heart failure(HF).However,the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported,which might be covered by the globe effects of it on the heart.In the current study,Langendorff system was applied to isolate card io myocytes(CMs)and cardiac fibroblasts(CFs)from transverse aortic constriction(TAC)-induced mice.Slight increase of miR-320 expression was observed in the whole heart tissue of TAC mice.Interestingly,miR-320 was significantly elevated in CMs but decreased in CFs from TAC mice at different time points.Then,recombinant adeno-associated virus 9 with cell-type-specific promoters were used to manipulate miR-320 expressions in vivo.Both in vitro and in vivo experiments showed the miR-320 overexpression in CMs exacerbated cardiac dysfunction,whereas overexpression of miR-320 in CFs alleviated cardiac fibrosis and hypertrophy.Mechanically,downstream signaling pathway analyses revealed that miR-320 might induce various effects via targeting PLEKHM3 and IFITM1 in CMs and CFs,respectively.Moreover,miR-320 mediated effects could be abolished by PLEKHM3 re-expression in CMs or IFITM1 re-expression in CFs.Interestingly,miR-320 treated CFs were able to indirectly affect CMs function,but not vice versa.Meanwhile,upstream signaling pathway analyses showed that miR-320 expression and decay rate were rigorously manipulated by Ago2,which was regulated by a cluster of cell-type-specific TFs distinctively expressed in CMs and CFs,respectively.Together,we demonstrated that miR-320 functioned differently in various cell types of the heart during the progression of HF.

关键词： miR elevated transverse

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Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-βpathway

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1732-1743页

作者： Xiaoxue Yang Liping Ma Rong Wei Tinghong Ye JianKang Zhou Maoyao Wen Ruoting Men Rami I.Aqeilan Yong Peng Li Yang Department of Gastroenterology&Hepatology West China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Biotherapy and Cancer Centre West China HospitalSichuan Universityand Collaborative Innovation Centre for BiotherapyChengdu 610041China School of Bioscience and Technology Chengdu medical collegeChengdu 610500China Department of Immunology&Cancer Research Hebrew University-Hadassah Medical SchoolJerusalemIsrael

The activation of hepatic stellate cells(HSCs)participates in liver fibrosis,and emerging evidences indicate that microRNAs(miRNAs)are abnormally expressed during HSC activation.However,the potential roles of miRNAs in liver fibrosis still remain elusive.Therefore,this study aimed to investigate the role of miR-199a-3p in liver fibrosis and its underlying mechanism.We found that miR-199a-3p expression was dramatically upregulated during HSC activation in vitro,and during liver fibrogenesis in CCl4-treated rats,and its liver expression was increased in the patients with cirrhosis.By the luciferase assay and RT-qPCR,we revealed that the expression of miR-199a-3p in HSCs was driven by the transcription factor Twist1 which could be further induced by TGF-βtreatment.Functional studies showed that inhibition of miR-199a-3p in both human LX2 cells and rat HSCs significantly decreased the expression of fibrotic markers,such as fibronectin and connective tissue growth factor(CTGF),whereas the forced expression of miR-199a-3p exhibited opposite effects,demonstrating the role of miR-199a-3p in promoting HSC activation.Mechanistically,miR-199a-3p plays an important role in TGF-βsignalling pathway activation through targeting CAV2 that negatively regulates the expression of transforming growth factor-beta receptor type I(TGFβRI).Importantly,administration of antagomiR-199a-3p in the CCl4-treated mice significantly ameliorated hepatic fibrosis.In conclusion,Twist1-induced miR-199a-3p mediates the activation of HSCs by suppressing CAV2 expression and subsequently increasing TGFβRI expression to promote TGF-βpathway.Our findings highlight the therapeutic potential of miR-199a-3p for hepatic fibrosis.

关键词： Twist1 miR hepatic

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miR-410 induces both epithelial–mesenchymal transition and radioresistance through activation of the PI3K/mTOR pathway in non-small cell lung cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1641-1654页

作者： Yue Yuan Hu Liao Qiang Pu Xixian Ke Xueting Hu Yongfang Ma Xinmei Luo Qianqian Jiang Yi Gong Min Wu Lunxu Liu Wen Zhu State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduSichuanChina Department of Thoracic Surgery West China HospitalSichuan UniversityChengduSichuanChina Department of Biomedical Sciences University of North DakotaGrand ForksNorth DakotaUSA

Radiotherapy remains one of the major treatments for non-small cell lung cancer(NSCLC)patients;whereas intrinsic or acquired radioresistance limits its efficacy.Nevertheless,most studies so far have only focused on acquired resistance.The exact mechanisms of intrinsic radioresistance in NSCLC are still unclear.A few studies have suggested that epithelial–mesenchymal transition(EMT)is associated with radioresistance in NSCLC.However,little is known about whether the abnormal expression of specific microRNAs induces both EMT and radioresistance.We previously found that miR-410 has multiple roles as an oncomiRNA in NSCLC.In this study,we revealed that miR-410 overexpression promoted EMT and radioresistance,accompanied by enhanced DNA damage repair both in vitro and in vivo.Conversely,knockdown of miR-410 showed the opposite effects.We further demonstrated that PTEN was a direct target of miR-410 by using bioinformatic tools and dual-luciferase reporter assays,and the miR-410-induced EMT and radioresistance were reversed by PI3K,Akt,and mTOR inhibitors or by restoring the expression of PTEN in NSCLC cells.In addition,we preliminarily found that the expression of miR-410 was positively correlated with EMT and negatively associated with the expression of PTEN in NSCLC specimens.In summary,these results demonstrated that miR-410 is an important regulator on enhancing both NSCLC EMT and radioresistance by targeting the PTEN/PI3K/mTOR axis.The findings suggest that miR-410-induced EMT might significantly contribute to the enhanced radioresistance.Therefore,miR-410 may serve as a potential biomarker or therapeutic target for NSCLC radiotherapy.

关键词： miR resistance transition

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circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

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International Journal of Oral Science 2022年第3期14卷 360-370页

作者： Liyuan Yu Kai Xia Jing Zhou Zhiai Hu Xing Yin Chenchen Zhou Shujuan Zou Jun Liu State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Orthodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Stomatology Kunming Yan’an hospitalKunmingChina State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Human adipose-derived stem cells(hASCs)are a promising cell type for bone tissue regeneration.Circular RNAs(circRNAs)have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis.However,how circRNAs regulate hASCs in osteogenesis is still unclear.Herein,we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs.Knockdown of circ_0003204 by si RNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs.We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p.We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 m RNA.The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis.Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model,while overexpression of circ_0003204 inhibited bone defect repair.Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

关键词： regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis miR

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Observation and analysis of atmospheric volatile organic compounds in a typical petrochemical area in Yangtze River Delta, China

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Journal of Environmental Sciences 2018年第9期30卷 233-248页

作者： Yunchen Zhang Rui Li Hongbo Fu Dong Zhou Jianmin Chen Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention Department of Environmental Science & Engineering Fudan University Shanghai 200433 China Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092 China Collaborative Innovation Center of Atmospheric Environment and Equipment Technology (CICAEET) Nanjing University of Information Science and Technology Nanjing 210044 China

Volatile organic compounds （VOCs） are a kind of important precursors for ozone photochemical formation. In this study, VOCs were measured from November 5th, 2013 to January 6th, 2014 at the Second Jinshan Industrial Area, Shanghai, China. The results showed that the measured VOCs were dominated by alkanes （41.8%）, followed by aromatics （20.1%）, alkenes （17.9%）, and halo-hydrocarbons （12.5%）. The daily trend of the VOC concentration showed a bimodal feature due to the rush-hour traffic in the morning and at nightfall. Based on the VOC concentration, a receptor model of Positive Matrix Factorization （PMF） coupled with the information related to VOC sources was applied to identify the major VOC emissions. The result showed five major VOC sources： solvent use and industrial processes were responsible for about 30% of the ambient VOCs, followed by rubber chemical industrial emissions （23%）, refinery and petrochemical industrial emissions （21%）, fuel evaporations （13%） and vehicular emissions （13%）. The contribution of generalized industrial emissions was about 74% and significantly higher than that made by vehicle exhaust. Using a propylene-equivalent method, alkenes displayed the highest concentra-tion, followed by aromatics and alkanes. Based on a maximum incremental reactivity （miR） method, the average hourly ozone formation potential （OFP） of VOCs is 220.49 ppbv. The most significant source for ozone chemical formation was identified to be rubber chemical industrial emissions, following one by vehicular emission. The data shown herein may provide useful information to develop effective VOC pollution control strategies in industrialized area.

关键词： VOCs PMF Emission sources Photochemical reactivity miR OFP

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Circulating endothelial microvesicles and their carried miR-125a 5p:potential biomarkers for ischaemic stroke

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Stroke & Vascular Neurology 2023年第2期8卷 89-102页

作者： Xiaotang Ma Xiaorong Liao Jiehong Liu Yan Wang Xiang Wang Yanfang Chen Xiaojian Yin Qunwen Pan Department of Neurology Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Pharmacology and Toxicology Wright State University Boonshoft School of MedicineDaytonOhioUSA

Background Endothelial microvesicles(EMVs)are closely associated with the status of endothelial cells(ECs).Our earlier study has shown that EMVs could exert protective roles in ECs by transferring their carried miR-125a 5p.However,whether circulating EMVs and their carried miR-125a 5p can be used as biomarkers in ischaemic stroke(IS)are remain unknown.Methods We recruited 72 subjects with IS,60 subjects with high stroke risk and 56 age-matched controls.The circulating EMVs and their carried miR-125a 5p(EMV-miR 125a 5p)levels were detected.We used microRNA(miR)array to study expression changes of miRs in plasma EMVs samples of three IS patients and three matched healthy controls.Transient middle cerebral artery occlusion(tMCAO)was used to establish IS mouse model.Results EMVs level was obviously elevated in IS patients,with the highest level in acute stage,and was positively related to carotid plaque,carotid intima-media thickness(IMT),National Institutes of Health Stroke Scale(NIHSS),infarct volume.On the contrary,we observed that EMV-miR 125a 5p level was obviously reduced in IS,with the lowest level in acute stage,and was negatively correlated with carotid plaque,IMT,NIHSS scores,infarct volume.EMVs and EMV-miR 125a 5p levels were closely related with large artery atherosclerosis subgroup.Importantly,EMVs and EMV-miR 125a 5p levels could serve as independent risk factors,and receiver operating characteristic curve achieved an area under curve(AUC)of 0.720 and 0.832 for IS,respectively,and elevated to 0.881 after their combination.In IS mouse model,control EMVs or n-EMVs administration could decrease the infarct volume and neurological deficit score,while increase the cerebral blood flow of IS mice compared with vehicle group,while IS EMVs or oxygen and glucose deprivation(OGD)-EMVs administration aggravated the tMCAO induced ischaemic injury.In addition,we observed that OGD EMVmiR-125a 5p could partially ameliorate the OGD EMVs induced brain injury after IS.Conclusions These findings demonstrate that circulatin

关键词： miR elevated protective

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伴多层菊形团胚胎性肿瘤的分子生物学改变研究现状

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中华神经外科杂志 2022年第1期38卷 104-106页

作者：赵恒马杰上海交通大学医学院附属新华医院儿神经外科 200092

伴多层菊形团胚胎性肿瘤(ETMR)是一种高度恶性的颅内肿瘤,19号染色体上miRNA簇(C19MC)的扩增是其重要的分子生物学特征。此外,包括miR17HG扩增、DICER突变、LIN28A高表达等在内的其他分子生物学改变可能均有助于ETMR的诊断和治疗。本文... 详细信息

伴多层菊形团胚胎性肿瘤(ETMR)是一种高度恶性的颅内肿瘤,19号染色体上miRNA簇(C19MC)的扩增是其重要的分子生物学特征。此外,包括miR17HG扩增、DICER突变、LIN28A高表达等在内的其他分子生物学改变可能均有助于ETMR的诊断和治疗。本文针对ETMR的分子生物学改变研究现状进行综述。

关键词：胚胎性肿瘤颅内肿瘤菊形团分子生物学诊断和治疗 miR 高度恶性研究现状

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Hsa-miR-186在结肠癌细胞中的表达及作用

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南方医科大学学报 2013年第5期33卷 654-660页

作者：陈芳周畅陆艳霞袁理彭皤莉郑林李学农南方医科大学基础医学院病理学系//广东省分子肿瘤病理学重点实验室广东广州510515

目的检测hsa-miR-186在结肠癌组织及细胞中的表达,探讨hsa-miR-186对结肠癌细胞生物学特性的影响及作用。方法应用实时荧光定量PCR检测了miR-186在12对配对的结肠癌组织、癌旁组织和5株结肠癌细胞中的表达情况;扩增包含miR-186前体序列... 详细信息

目的检测hsa-miR-186在结肠癌组织及细胞中的表达,探讨hsa-miR-186对结肠癌细胞生物学特性的影响及作用。方法应用实时荧光定量PCR检测了miR-186在12对配对的结肠癌组织、癌旁组织和5株结肠癌细胞中的表达情况;扩增包含miR-186前体序列在内的基因片段,并将其克隆至PLVYHM载体,将PLVTHM-miR186质粒转染SW620细胞,流式分选慢病毒感染的SW620细胞;CCK-8法、划痕实验和Transwell检测细胞检测细胞的增殖、迁移和侵袭能力。Western Blot检测靶基因YY1蛋白水平的表达。结果与癌组织相比,12例癌组织中miR-186的平均表达量为0.0024±0.0027-显著低于癌旁组织的0-066±0.068,P=0.008;miR-186在高转移潜能的人结肠癌细胞SW620和LOVO相对表达量分别为0.118±0.138和0.157±0.001,与在低转移潜能HT-29细胞中表达量1.000±0.00,差异具有统计学意义PmiRl86重组质粒构建成功;荧光定量PCR表明稳定过表达miR-186的结肠癌细胞株SW620构建成功,且过表达miR-186后降低了细胞的增殖、迁移及侵袭能力,差异均具有统计学意义PmiR-186的细胞中,miR-186的表达明显高于对照组和未处理组,YY1蛋白质水平有所下降。结论 hsa-miR-186在结肠癌组织以及在高转移潜能的人结肠癌细胞SW620、L0VO中低表达,具有类似抑癌基因的作用;成功构建PLVTHM-miR186慢病毒重组质粒,并稳定转染结肠癌细胞SW620,抑制了细胞的增殖、迁移和侵袭能力。miR-186调控YY1表达可能是抑制结直肠癌生物特性的重要机制之一。

关键词：结肠癌细胞 hsa miR 186 慢病毒增殖迁移侵袭

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