This study aimed to assess the role of microRNAs(miRNAs)in regulating monocarboxylate transporter-1(MCT1)expression in rat brain after permanent focal cerebral ischemia to identify a new target for early treatment of ...This study aimed to assess the role of microRNAs(miRNAs)in regulating monocarboxylate transporter-1(MCT1)expression in rat brain after permanent focal cerebral ischemia to identify a new target for early treatment of cerebral ischemia.Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion(pMCAO)in rats.Morphology and protein expression levels of MCT1 were assessed by immunofluorescence and Western blotting.Using bioinformatics and double luciferase reporter assays,rno-miR-124-3p was selected as a direct target for rat MCT1.Expression of rno-miR-124-3p after pMCAO was detected.Then,rats were treated with rno-miR-124-3p agomir via lateral ventricle injection,and after 6 h or 24 h ischemia,rno-miR-124-3p expression and gene and protein expression of MCT-1 were detected by qRT-PCR and Western blotting.Brain infarction was identified by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Results showed that pMCAO induced brain infarction and increased the expression of MCT1.The levels of rno-miR-124-3p after pMCAO were in contrast to those of MCT1 protein in ischemic region,while declined after 3,6 and 12 h of pMCAO in ischemic penumbra.After administration of rno-miR-124-3p agomir,MCT1 mRNA and protein levels were increased after 6 h of pMCAO,while decreased after 24 h of pMCAO.Meanwhile,rno-miR-124-3p levels increased after both times.TTC staining showed treatment with rno-miR-124-3p agomir reduced brain infarction.The role of rno-miR-124-3p in regulating MCT1 was as a positive regulator after 6 h of pMCAO,while a negative regulator after 24 h of pMCAO,however,both activities had protective effects against cerebral ischemia.展开更多
Urothelial bladder carcinoma(UBC)is an intricate malignancy with a variable natural history and clinical behavior.Despite developments in diagnosis/prognosis refi nement and treatment modalities,the recurrence rate is...Urothelial bladder carcinoma(UBC)is an intricate malignancy with a variable natural history and clinical behavior.Despite developments in diagnosis/prognosis refi nement and treatment modalities,the recurrence rate is high,and progression from non-muscle to muscle invasive UBC commonly leads to metastasis.Moreover,patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment,and overall survival rates are poor.Thus,UBC remains a challenge in the oncology fi eld,representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence,progression,and chemo-refractoriness.However,progress toward personalized medicine has been hampered by the unique genetic complexity of UBC.Recent genome-wide expression and sequencing studies have brought new insights into its molecular features,pathogenesis and clinical diversity,revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups.Hence,it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation.In this review,we have summarized ours and others’research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer:tumor neovascularization,invasion and metastasis,and energy metabolism reprogramming of the tumor microenvironment.展开更多
Monocarboxylate transporters（MCTs）, which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ...Monocarboxylate transporters（MCTs）, which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning（IPC） on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups（sham-operated group, ischemia only group, IPC ＋ sham-operated group and IPC ＋ ischemia group）. A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region（CA1）, not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC ＋ ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC ＋ sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC ＋ ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia.展开更多
文摘This study aimed to assess the role of microRNAs(miRNAs)in regulating monocarboxylate transporter-1(MCT1)expression in rat brain after permanent focal cerebral ischemia to identify a new target for early treatment of cerebral ischemia.Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion(pMCAO)in rats.Morphology and protein expression levels of MCT1 were assessed by immunofluorescence and Western blotting.Using bioinformatics and double luciferase reporter assays,rno-miR-124-3p was selected as a direct target for rat MCT1.Expression of rno-miR-124-3p after pMCAO was detected.Then,rats were treated with rno-miR-124-3p agomir via lateral ventricle injection,and after 6 h or 24 h ischemia,rno-miR-124-3p expression and gene and protein expression of MCT-1 were detected by qRT-PCR and Western blotting.Brain infarction was identified by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Results showed that pMCAO induced brain infarction and increased the expression of MCT1.The levels of rno-miR-124-3p after pMCAO were in contrast to those of MCT1 protein in ischemic region,while declined after 3,6 and 12 h of pMCAO in ischemic penumbra.After administration of rno-miR-124-3p agomir,MCT1 mRNA and protein levels were increased after 6 h of pMCAO,while decreased after 24 h of pMCAO.Meanwhile,rno-miR-124-3p levels increased after both times.TTC staining showed treatment with rno-miR-124-3p agomir reduced brain infarction.The role of rno-miR-124-3p in regulating MCT1 was as a positive regulator after 6 h of pMCAO,while a negative regulator after 24 h of pMCAO,however,both activities had protective effects against cerebral ischemia.
文摘Urothelial bladder carcinoma(UBC)is an intricate malignancy with a variable natural history and clinical behavior.Despite developments in diagnosis/prognosis refi nement and treatment modalities,the recurrence rate is high,and progression from non-muscle to muscle invasive UBC commonly leads to metastasis.Moreover,patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment,and overall survival rates are poor.Thus,UBC remains a challenge in the oncology fi eld,representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence,progression,and chemo-refractoriness.However,progress toward personalized medicine has been hampered by the unique genetic complexity of UBC.Recent genome-wide expression and sequencing studies have brought new insights into its molecular features,pathogenesis and clinical diversity,revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups.Hence,it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation.In this review,we have summarized ours and others’research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer:tumor neovascularization,invasion and metastasis,and energy metabolism reprogramming of the tumor microenvironment.
基金supported by a Priority Research Centers Program grant(NRF-2009-0093812)through the National Research Foundation of Korea funded by the Ministry of Science,ICT and Future Planningby 2014 Research Grant from Kangwon National University
文摘Monocarboxylate transporters（MCTs）, which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning（IPC） on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups（sham-operated group, ischemia only group, IPC ＋ sham-operated group and IPC ＋ ischemia group）. A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region（CA1）, not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC ＋ ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC ＋ sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC ＋ ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia.
