Gastric cancer(GC)is a prevalent malignant tumor globally,with high incidence and mortality rates.Advances in understanding molecular mechanisms underlying GC have highlighted the role of microRNAs(miRNAs)in its initi...Gastric cancer(GC)is a prevalent malignant tumor globally,with high incidence and mortality rates.Advances in understanding molecular mechanisms underlying GC have highlighted the role of microRNAs(miRNAs)in its initiation,progression,and treatment.The Let-7 family,an important class of miRNAs,is closely associated with the biological behaviors of GC.Aberrant expression of various Let-7 family members in GC patients contributes to disease progression,as they target multiple molecular pathways and participate in diverse regulatory mechanisms throughoutGCpathogenesis.This article systematically summarizes the expression patterns of Let-7 familymembers in GC,explores their influence onGCcell behaviors such as proliferation,invasion,andmetastasis through key target gene regulation,and reviews current advances in Let-7-based interventions forGC treatment.It aims to provide foundational insights for a deeper understanding of Let-7-related mechanisms in GC and optimize therapeutic strategies.展开更多
BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),wh...BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),which constitute a cellfree therapeutic approach,have garnered extensive attention in alleviating HIRI.However,the potential of hucMSC-exos in mitigating apoptosis and their underlying mechanisms remain largely unknown.AIM To investigate the effects of hucMSC-exos on apoptosis after HIRI and explore the underlying mechanisms.METHODS The therapeutic effects of hucMSC-exos on HIRI and hypoxia/reoxygenation injury in L02 cells were investigated.RNA sequencing was used to detect differentially expressed genes in L02 cells after hucMSC-exo treatment,and the expression of apoptosis markers in L02 cells was analyzed.MicroRNA(miRNA)sequencing was performed to analyse the miRNA expression profiles of hucMSCexos and L02 cells after hucMSC-exo treatment.Through a miRNA-mRNA integrated analysis,candidate miRNAs and their regulated target genes were identified.We subsequently studied the roles of these candidate miRNAs in mouse HIRI and L02 cell hypoxia/reoxygenation injury.RESULTSFluorescence confocal microscopy revealed that hucMSC-exos effectively homed to the liver and were taken up byhepatocytes, likely due to the presence of anti-very late antigen-4 and anti-lymphocyte function-associated antigen-1 on the surface of hucMSC-exos. HucMSC-exos alleviate hepatocyte damage by inhibiting apoptosis. Specifically,let-7i-5p within hucMSC-exos inhibited the expression of the factor-related apoptosis ligand protein in L02 cells,leading to the upregulation of B-cell lymphoma-2 and the downregulation of B-cell lymphoma-2-associated Xprotein and cysteinyl aspartate specific proteinase-3, thereby inhibiting L02 cell apoptosis and enhancing cellproliferation activity. The overexpression of let-7i-5p effectively enhanced the antiapoptotic effects of hucMSC-exosboth in vitro and in vivo.CONCLUSIONOur findings indicate that hucMSC-exos alleviate HIRI by inhibiting apoptosis. We demonstrated that hucMSCexostarget apoptosis in L02 cells and mediate the let-7i-5p/factor-related apoptosis ligand pathway, therebyameliorating HIRI. This study provides new insights into the role of hucMSC-exos in hepatocyte apoptosis andhighlights the potential of hucMSC-exos as a therapeutic strategy for HIRI.展开更多
基金financed by grants from the Hunan Province Foundation of High-Level Health Talent(225 Program,20231526)the Natural Science Foundation of Hunan Province(2025JJ81050).
文摘Gastric cancer(GC)is a prevalent malignant tumor globally,with high incidence and mortality rates.Advances in understanding molecular mechanisms underlying GC have highlighted the role of microRNAs(miRNAs)in its initiation,progression,and treatment.The Let-7 family,an important class of miRNAs,is closely associated with the biological behaviors of GC.Aberrant expression of various Let-7 family members in GC patients contributes to disease progression,as they target multiple molecular pathways and participate in diverse regulatory mechanisms throughoutGCpathogenesis.This article systematically summarizes the expression patterns of Let-7 familymembers in GC,explores their influence onGCcell behaviors such as proliferation,invasion,andmetastasis through key target gene regulation,and reviews current advances in Let-7-based interventions forGC treatment.It aims to provide foundational insights for a deeper understanding of Let-7-related mechanisms in GC and optimize therapeutic strategies.
基金Supported by Natural Science Foundation Project of Yunnan Province,No.202302AA310025 and No.202449CE340016Health Research Project of Yunnan Province,No.300068.
文摘BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),which constitute a cellfree therapeutic approach,have garnered extensive attention in alleviating HIRI.However,the potential of hucMSC-exos in mitigating apoptosis and their underlying mechanisms remain largely unknown.AIM To investigate the effects of hucMSC-exos on apoptosis after HIRI and explore the underlying mechanisms.METHODS The therapeutic effects of hucMSC-exos on HIRI and hypoxia/reoxygenation injury in L02 cells were investigated.RNA sequencing was used to detect differentially expressed genes in L02 cells after hucMSC-exo treatment,and the expression of apoptosis markers in L02 cells was analyzed.MicroRNA(miRNA)sequencing was performed to analyse the miRNA expression profiles of hucMSCexos and L02 cells after hucMSC-exo treatment.Through a miRNA-mRNA integrated analysis,candidate miRNAs and their regulated target genes were identified.We subsequently studied the roles of these candidate miRNAs in mouse HIRI and L02 cell hypoxia/reoxygenation injury.RESULTSFluorescence confocal microscopy revealed that hucMSC-exos effectively homed to the liver and were taken up byhepatocytes, likely due to the presence of anti-very late antigen-4 and anti-lymphocyte function-associated antigen-1 on the surface of hucMSC-exos. HucMSC-exos alleviate hepatocyte damage by inhibiting apoptosis. Specifically,let-7i-5p within hucMSC-exos inhibited the expression of the factor-related apoptosis ligand protein in L02 cells,leading to the upregulation of B-cell lymphoma-2 and the downregulation of B-cell lymphoma-2-associated Xprotein and cysteinyl aspartate specific proteinase-3, thereby inhibiting L02 cell apoptosis and enhancing cellproliferation activity. The overexpression of let-7i-5p effectively enhanced the antiapoptotic effects of hucMSC-exosboth in vitro and in vivo.CONCLUSIONOur findings indicate that hucMSC-exos alleviate HIRI by inhibiting apoptosis. We demonstrated that hucMSCexostarget apoptosis in L02 cells and mediate the let-7i-5p/factor-related apoptosis ligand pathway, therebyameliorating HIRI. This study provides new insights into the role of hucMSC-exos in hepatocyte apoptosis andhighlights the potential of hucMSC-exos as a therapeutic strategy for HIRI.
