Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-in...Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.展开更多
BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying...BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying mechanisms of miR-136 during this process.AIM To investigate the role of miR-136 in H.pylori-induced GC progression.METHODS GC and gastric epithelial cells were infected with H.pylori and transfected with miR-136 mimic,inhibitor,mimic plus PDCD11(identified as miR-136 target),or miR-NC(control).Cell proliferation,migration,and invasion were assessed via cell counting kit-8 assay,colony formation,wound healing,and Transwell assays.Nuclear factor kappa-B(NF-κB)/miR-136/PDCD11 interactions were confirmed by luciferase and inhibition assays.For in vivo studies H.pylori-infected BGC-823 cells were injected into nude mice.Reverse transcription PCR,western blot,immunohistochemistry,and immunofluorescent staining assay were used to assess mRNA and protein expression.RESULTS miR-136 expression was significantly upregulated while PDCD11 expression was significantly downregulated in early GC tissues and GC cells infected with H.pylori compared with non-infected tissues or cells(all P<0.01).miR-136 overexpression induced by H.pylori could promote the proliferation and migration of infected GC cells and induce the growth of H.pylori-positive GC tumors in mice while its inhibition could reverse this effect.Mechanistically,upregulation of miR-136 suppressed PDCD11 through NF-κB activation induced by H.pylori infection.CONCLUSION miR-136 is a novel diagnostic biomarker and therapeutic target in H.pylori-associated early-stage gastric carcinogenesis and acts through the NF-κB-miR-136-PDCD11 pathway.展开更多
The study by Chen et al found that miR-136 plays an indispensable role in the inflammation-cancer transformation in gastric cancer(GC).The authors conducted in vivo and in vitro experiments and verified them in conjun...The study by Chen et al found that miR-136 plays an indispensable role in the inflammation-cancer transformation in gastric cancer(GC).The authors conducted in vivo and in vitro experiments and verified them in conjunction with functional and molecular mechanisms.Their key findings indicate that Helicobacter pylori(H.pylori)activated NF-κB/miR-136/PDCD11 axis to induce the growth of H.pylori-positive GC tumors.And miR-136 is markedly associated with characteristics related to the gastric mucosal histopathological,supporting its use as a diagnostic biomarker and a therapeutic target for early H.pylori-induced GC.Chronic inflammation is one of the important precancerous lesions.With the development of emerging technologies such as multi-omics technology,the pathways linking chronic inflammation to cancer have been extensively elucidated.In this letter,we focus on introducing the molecular mechanisms of chronic inflammation in the development of GC,which will provide new insights for early diagnosis,personalized treatment,and prognosis assessment of GC.展开更多
基金supported by grants from the Knut and Alice Wallenberg foundation(P-OB,JRZ,and AK)the Swedish Research Council(JRZ and AK),Centrum för idrottsforskning(AK and JRZ)+7 种基金the NovoNordisk Foundation Metabolic Stress Associated Molecules(MSAM)consortium NNF15SA0018346 and Metabolite-related Inflammation and Disease(MeRIAD)consortium Grant number 0064142(AK)the Swedish Diabetes Foundation(AK and JRZ)the European Foundation for the Study of Diabetes(JRZ and AK)the Region Stockholm(ALF project)(JRZ and KC)the Strategic Research Program in Diabetes at Karolinska Institutet(JRZ and AK)supported by the Strategic Research Programme in Diabetes(SRP Diabetes)for use of the Seahorse flux analyzer.Human islets were made possible through the Juvenile Diabetes Research Foundation(JDRF)award 31-2008-416(European Coordinating Infrastructure for Islet Transplantation(ECIT),Islet for Basic Research program)AK holds a Distinguished Investigator Grant within Endocrinology and Metabolism from the Novo Nordisk Foundation(NNF24OC0088739)JRZ received the 2024 European Association for the Study of Diabetes(ESAD)-Novo Nordisk Foundation Diabetes Prize for Excellence(NNF24SA0092609).
文摘Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.
基金Supported by the National Natural Science Foundation of China,No.82470593General Project of the Development Fund of the Affiliated Hospital of Xuzhou Medical University,No.XYFM202334.
文摘BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying mechanisms of miR-136 during this process.AIM To investigate the role of miR-136 in H.pylori-induced GC progression.METHODS GC and gastric epithelial cells were infected with H.pylori and transfected with miR-136 mimic,inhibitor,mimic plus PDCD11(identified as miR-136 target),or miR-NC(control).Cell proliferation,migration,and invasion were assessed via cell counting kit-8 assay,colony formation,wound healing,and Transwell assays.Nuclear factor kappa-B(NF-κB)/miR-136/PDCD11 interactions were confirmed by luciferase and inhibition assays.For in vivo studies H.pylori-infected BGC-823 cells were injected into nude mice.Reverse transcription PCR,western blot,immunohistochemistry,and immunofluorescent staining assay were used to assess mRNA and protein expression.RESULTS miR-136 expression was significantly upregulated while PDCD11 expression was significantly downregulated in early GC tissues and GC cells infected with H.pylori compared with non-infected tissues or cells(all P<0.01).miR-136 overexpression induced by H.pylori could promote the proliferation and migration of infected GC cells and induce the growth of H.pylori-positive GC tumors in mice while its inhibition could reverse this effect.Mechanistically,upregulation of miR-136 suppressed PDCD11 through NF-κB activation induced by H.pylori infection.CONCLUSION miR-136 is a novel diagnostic biomarker and therapeutic target in H.pylori-associated early-stage gastric carcinogenesis and acts through the NF-κB-miR-136-PDCD11 pathway.
基金Supported by National Natural Science Foundation of China,No.32270768,No.82273970,and No.82370715。
文摘The study by Chen et al found that miR-136 plays an indispensable role in the inflammation-cancer transformation in gastric cancer(GC).The authors conducted in vivo and in vitro experiments and verified them in conjunction with functional and molecular mechanisms.Their key findings indicate that Helicobacter pylori(H.pylori)activated NF-κB/miR-136/PDCD11 axis to induce the growth of H.pylori-positive GC tumors.And miR-136 is markedly associated with characteristics related to the gastric mucosal histopathological,supporting its use as a diagnostic biomarker and a therapeutic target for early H.pylori-induced GC.Chronic inflammation is one of the important precancerous lesions.With the development of emerging technologies such as multi-omics technology,the pathways linking chronic inflammation to cancer have been extensively elucidated.In this letter,we focus on introducing the molecular mechanisms of chronic inflammation in the development of GC,which will provide new insights for early diagnosis,personalized treatment,and prognosis assessment of GC.
