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Genes & Diseases 2024年第3期11卷 98-101页

作者： Zishuai Wang Yilong Yao Xinhua Hou Danyang Fan Yanwen Liu Adeyinka Abiola Adetula Yalan Yang kui Li Zhonglin Tang Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenGuangdong518000China Kunpeng Institute of Modern Agriculiture at Foshan Chinese Academy of Agricultural SciencesFoshanGuangdong528226China GuangXi Engineering Centre for Resource Development of Bama Xiang Pig BamaGuangxi 547500China Institute of Animal Science Chinese Academy of Agricultural SciencesBeijing100193China

Aerobic exercise training alters gene expression in skeletal muscle,and mirNAs significantly contribute to motion ***,the molecular mechanisms by which mirNAs regulate the response to exercise training are not well ***,we found that the abundance of mir-378a-3p in skeletal muscle significantly decreased after exercise ***-378a-3p knockout mice showed increased insulin sensitivity,insulin-mediated glucose uptake.

关键词： skeletal mir uptake

mir-140-3p enhanced the osteo/odontogenic differentiation of DPSCs via inhibiting KMT5B under hypoxia condition

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International Journal of Oral Science 2021年第4期13卷 398-407页

作者： Han Zheng Ning Wang Le Li Lihua Ge Haichao Jia Zhipeng Fan Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionCapital Medical University School of StomatologyBeijingChina Tsinghua University Hospital Stomatological Disease Prevention and Control CenterTsinghua UniversityBeijingChina Department of Orthodontics Capital Medical University School of StomatologyBeijingChina Research Unit of Tooth Development and Regeneration Chinese Academy of Medical SciencesBeijingChina

Human dental pulp stem cells(DPSCs)have emerged as an important source of stem cells in the tissue engineering,and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue ***,little is known about the complicated molecular *** this study,we aimed to investigate the influence and mechanism of mir-140-3p on DPSCs under hypoxia *** was induced in DPSCs by Cobalt chloride(CoCl_(2))*** osteo/dentinogenic differentiation capacity of DPSCs was assessed by alkaline phosphatase(ALP)activity,Alizarin Red S staining and main osteo/dentinogenic markers.A luciferase reporter gene assay was performed to verify the downstream target gene of *** research exhibited that mir-140-3p promoted osteo/dentinogenic differentiation of DPSCs under normoxia ***,mir-140-3p rescued the CoCl_(2)-induced decreased osteo/odontogenic differentiation potentials in ***,we investigated that mir-140-3p directly targeted lysine methyltransferase 5B(KMT5B).Surprisingly,we found inhibition of KMT5B obviously enhanced osteo/dentinogenic differentiation of DPSCs both under normoxia and hypoxia *** conclusion,our study revealed the role and mechanism of mir-140-3p for regulating osteo/dentinogenic differentiation of DPSCs under hypoxia,and discovered that mir-140-3p and KMT5B might be important targets for DPSC-mediated tooth or bone tissue regeneration.

关键词： DPSCs mir inhibiting

mir-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD^(+)/SIRT inactivation

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1181-1193页

作者： Hui Gong Honghan Chen Peng Xiao Ning Huang Xiaojuan Han Jian Zhang Yu Yang Tiepeng Li Tingting Zhao Haoran Tai Weitong Xu Gongchang Zhang Chuhui Gong Ming Yang Xiaoqiang Tang Hengyi Xiao The Lab of Aging Research National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan University1 Keyuan 4 RoadGaopeng AvenueChengdu 610093China Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengdu 610041China

Nicotinamide adenine dinucleotide(NAD^(+))is indispensable for the anti-aging activity of the sirtuin(SIRT)family *** protein kinase(AMPK)upregulates NAD^(+)synthesis and SIRT activity in a nicotinamide phosphoribosyltransferase(NAMPT)-dependent ***,the molecular mechanisms that affect AMPK-driven NAMPT expression and NAD^(+)/SIRT activation remain *** this study,we tried to identify senescence-associated microRNAs(mirNAs)that negatively regulate the cascade linking AMPK and NAMPT ***-screening experiments showed that the expression of mir-146a increased in senescent cells but decreased following AMPK ***,mir-146a overexpression weakened the metforminmediated upregulation of NAMPT expression,NAD^(+)synthesis,SIRT activity,and senescence protection,whereas treatment with the mir-146a inhibitor reversed this ***,these findings were observed both in vitro and in ***,mir146a directly targeted the 3′-UTR of Nampt mRNA to reduce the expression of *** activators metformin and 5-aminoimidazole-4-carboxamide(AICAR)hindered mir-146a expression at the transcriptional level by promoting IκB kinase(IKK)phosphorylation to attenuate nuclear factor-kappaB(NF-κB)*** findings identified a novel cascade that negatively regulates the NAD^(+)/SIRT pathway by suppressing mir-146a-mediated NAMPT ***,our results showed that mir-146a impedes the anti-aging effect of *** mutual inhibitory relationship between mir-146a and AMPK enriches our understanding of the molecular connections between AMPK and SIRT and provides new insight into mirNA-mediated NAD^(+)/SIRT regulation and an intervention point for the prevention of aging and age-related diseases.

关键词： mir NAMPT prevention

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 ***,most studies so far have only focused on acquired *** 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 ***,little is known about whether the abnormal expression of specific microRNAs induces both EMT and *** previously found that mir-410 has multiple roles as an oncomirNA in *** this study,we revealed that mir-410 overexpression promoted EMT and radioresistance,accompanied by enhanced DNA damage repair both in vitro and in ***,knockdown of mir-410 showed the opposite *** 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 *** 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 *** summary,these results demonstrated that mir-410 is an important regulator on enhancing both NSCLC EMT and radioresistance by targeting the PTEN/PI3K/mTOR *** findings suggest that mir-410-induced EMT might significantly contribute to the enhanced ***,mir-410 may serve as a potential biomarker or therapeutic target for NSCLC radiotherapy.

关键词： mir resistance transition

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 *** 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 ***,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

mir-124/VAMP3 is a novel therapeutic target for mitigation of surgical trauma-induced microglial activation

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Signal Transduction and Targeted Therapy 2019年第1期4卷 434-444页

作者： Yan Chen Jing-xian Sun Wan-kun Chen Gen-cheng Wu Yan-qing Wang Ke-ying Zhu Jun Wang Department of Integrative Medicine and Neurobiology State Key Laboratory of Medical NeurobiologySchool of Basic Medical ScienceFudan University200032 ShanghaiChina Institutes of Brain Science Collaborative Innovation Center for Brain ScienceFudan University200032 ShanghaiChina Institute of Acupuncture and Moxibustion Fudan Institutes of Integrative MedicineFudan University200032 ShanghaiChina Department of Anesthesiology Fudan University Shanghai Cancer Center200032 ShanghaiChina Department of Oncology Shanghai Medical CollegeFudan University200032 ShanghaiChina Department of Clinical Neuroscience Center for Molecular MedicineKarolinska Institutet17176 StockholmSweden

Activation of microglia and the subsequently elevated inflammatory cytokine release in the brain during surgery predispose individuals to cognitive dysfunction,also known as postoperative cognitive dysfunction(POCD).mir-124 is one of the most abundant microRNAs in the brain that regulates microglial *** the role of mir-124 in microglial activation in the context of surgery may therefore promote understanding of as well as therapeutic development for post-surgical disorders involving microglial *** downstream targets of mir-124 were investigated using bioinformatic screening and dual-luciferase reporter assay validation,and vesicle-associated membrane protein 3(VAMP3)was identified as a potential *** kinetics of mir-124/VAMP3 expression was first examined in vitro in microglial cells(primary microglia and BV2 microglial cells)following lipopolysaccharide(LPS)*** induced a time-dependent decrease of mir-124 and upregulated the expression of *** mir-124/VAMP3 expression by using mir-124 mimics or VAMP3-specific siRNA in LPS-stimulated BV2 microglial cells inhibited BV2 microglial activation-associated inflammatory cytokine *** further examine the role of mir-124/VAMP3 in a surgical setting,we employed a rat surgical trauma *** microglial activation and altered mir-124/VAMP3 expression were observed following surgical *** also altered mir-124/VAMP3 expression in the rat surgical trauma model by administration of exogenous mir-124 and by using electroacupuncture,which is a clinically applicable treatment that modulates microglial function and minimizes postoperative *** determined that electroacupuncture treatment specifically increases the expression of mir-124 in the hypothalamus and *** mir-124 expression with a concomitant decrease in VAMP3 expression resulted in decreased inflammatory cytokine release related to microglial activation *** s

关键词： mir surgical therapeutic

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 *** RNAs(circRNAs)have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell ***,how circRNAs regulate hASCs in osteogenesis is still ***,we found circ_0003204 was significantly downregulated during osteogenic differentiation of *** of circ_0003204 by si RNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of *** performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging *** predicted and confirmed that mir-370-3p had targets in the 3′-UTR of HDAC4 m *** following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via mir-370-3p/HDAC4 *** 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 *** 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

Bone-targeting engineered small extracellular vesicles carrying anti-mir-6359-CGGGAGC prevent valproic acid-induced bone loss

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Signal Transduction and Targeted Therapy 2024年第2期9卷 751-765页

作者： Xudong Xie Peng Cheng Liangcong Hu Wu Zhou Detai Zhang Samuel Knoedler Guodong Liu Yuan Xiong Hang Xue Yiqiang Hu Barbara Kern Doha Obed Adriana CPanayi Lang Chen Chenchen Yan Ze Lin Guandong Dai Bobin Mi Yingze Zhang Guohui Liu Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan 430022China Department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China Division of Plastic Surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02152USA Department of Plastic Surgery and Hand Surgery Klinikum Rechts der IsarTechnical University of MunichMunichGermany Medical Center of Trauma and War Injuries Daping HospitalArmy Medical UniversityChonqing 400042China Department of Plastic Surgery Campus CharitéMitte|Campus Virchow-KlinikumCharité-Universitätsmedizin Berlincorporate member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany Berlin Institute of Health Charité-Universitätsmedizin BerlinBerlinGermany Department of Plastic AestheticHand and Reconstructive SurgeryHannover Medical SchoolHannoverGermany Department of Hand Plastic and Reconstructive SurgeryMicrosurgeryBurn CenterBG Trauma Center LudwigshafenUniversity of HeidelbergLudwig-Guttmann-Strasse 1367071 Ludwigshafen/RhineGermany Pingshan District People’s Hospital of Shenzhen Pingshan General Hospital of Southern Medical UniversityShenzhenGuangdong 518118China Department of Orthopaedic Surgery The Third Hospital of Hebei Medical UniversityNO.139 Ziqiang RoadShijiazhuang 050051China

The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain ***,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and *** effect was attributed to VPA-induced elevation in osteoclast formation and *** RNA-sequencing,we observed a significant rise in precursor mir-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature mir-6359(mir-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and mir-6359 fluorescent in situ hybridization(mir-6359-FISH).Specifically,the mir-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive ***,VPA-induced mir-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone ***,there are no medications that can effectively treat VPA-induced bone ***,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-mir-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-mir-6359 *** confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.

关键词： mir protective stimulation

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 ***,whether circulating EMVs and their carried mir-125a 5p can be used as biomarkers in ischaemic stroke(IS)are remain *** We recruited 72 subjects with IS,60 subjects with high stroke risk and 56 age-matched *** circulating EMVs and their carried mir-125a 5p(EMV-mir 125a 5p)levels were *** used microRNA(mir)array to study expression changes of mirs in plasma EMVs samples of three IS patients and three matched healthy *** middle cerebral artery occlusion(tMCAO)was used to establish IS mouse *** 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 *** 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 *** and EMV-mir 125a 5p levels were closely related with large artery atherosclerosis ***,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 *** 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 *** addition,we observed that OGD EMVmir-125a 5p could partially ameliorate the OGD EMVs induced brain injury after ***

关键词： mir elevated protective

Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in mir-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo M.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and Molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor mir-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a mir-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in mir-15a downmodulated PDAC ***,we discovered that mir-15a repressed IGF1R expression via Fra-2 *** mir-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in mir-15a downmodulated PDAC.

关键词： IGF1R Fra mir