BACKGROUND Ectopic expression of miRNAs promotes tumor development and progression.miRNA(miR)-320a is downregulated in many cancers,including gastric cancer(GC).However,the mechanism underlying its downregulation and ...BACKGROUND Ectopic expression of miRNAs promotes tumor development and progression.miRNA(miR)-320a is downregulated in many cancers,including gastric cancer(GC).However,the mechanism underlying its downregulation and the role of miR-320a in GC are unknown.AIM To determine expression and biological functions of miR-320a in GC and investigate the underlying molecular mechanisms.METHODS Quantitative real-time polymerase chain reaction(PCR)was used to determine expression of miR-320a in GC cell lines and tissues.TargetScanHuman7.1,miRDB,and microRNA.org were used to predict the possible targets of miR-320a,and a dual luciferase assay was used to confirm the findings.Western blotting was used to detect the protein levels of pre-B-cell leukemia homeobox 3(PBX3)in GC cells and tissue samples.Cell Counting Kit-8 proliferation,Transwell,wound healing,and apoptosis assays were performed to analyze the biological functions of miR-320a in GC cells.Methylation-specific PCR was used to analyze the methylation level of the miR-320a promoter CpG islands.5-Aza-2’-deoxycytidine(5-Aza-CdR)and trichostatin A(TSA)were used to treat GC cells.RESULTS miR-320a expression was lower in GC cell lines and tissues than in the normal gastric mucosa cell line GES-1 and matched adjacent normal tissues.miR-320a overexpression suppressed GC cell proliferation,invasion and migration,and induced apoptosis.PBX3 was a target of miR-320a in GC.The methylation level of the miR-320a promoter CpG islands was elevated and this was partly reversed by 5-Aza-CdR and TSA.CONCLUSION miR-320a acts as a tumor suppressor and inhibits malignant behavior of GC cells,partly by targeting PBX3.DNA methylation is an important mechanism associated with low expression of miR-320a.展开更多
We rechecked the original data of Figure 3,Part.B,and found that 0 h group in the BGC-823 cell wound scratch assay was misapplied.Therefore,we are writing to apply for the modification of Figure 3,Part.B.
BACKGROUND Necrotizing enterocolitis(NEC)remains a prominent gastrointestinal emergency among infants,particularly term infants with congenital heart defects(CHD)being at high risk.The molecular processes that contrib...BACKGROUND Necrotizing enterocolitis(NEC)remains a prominent gastrointestinal emergency among infants,particularly term infants with congenital heart defects(CHD)being at high risk.The molecular processes that contribute to NEC have yet to be completely understood.The high mortality rates necessitate an active search for noninvasive biomarkers that can aid in the preclinical diagnosis and prognosis of NEC.MicroRNAs(miRs),which are involved in many biological processes in both health and disease,have been discovered to play an important role in regulating inflammation and immune responses via various signaling pathways.AIM To determine the plasma levels of miR-155,miR-221,miR-223,miR-320a,miR-451a as potential NEC biomarkers in term newborns with CHD.METHODS This prospective cohort study included twenty-tree term newborns with CHD who underwent cardiac surgery on the median day of life(DOL)=7.Nine of them developed NEC(Bell’s stage IIA and IIIA)within 1 week of cardiac surgery(NEC newborns).Blood samples were collected before(median DOL=5)and following(median DOL=13)cardiac surgery.Levels of plasma miR-155-5p,miR-221-3p,miR-223-3p,miR-320a-3p,and miR-451a were determined using real-time polymerase chain reaction.The functional analysis was executed using the DIANA-miRPath v4.0.RESULTS Preoperatively,NEC newborns had significantly lower plasma levels of miR-155(2.70-fold,P=0.020),miR-223(2.42-fold,P=0.030),and miR-320a(3.62-fold,P=0.006)than newborns without NEC.Postoperatively,miR-451a levels differed significantly between the newborn groups,showing a 4.70-fold decrease(P=0.014)in expression when clinical NEC symptoms appeared.According to receiver operating characteristic analysis,miR-320a was found to be the most effective predictive biomarker for NEC[area under the curve(AUC)=0.835,63%sensitivity,100%specificity],while miR-451a was identified as a NEC biomarker(AUC=0.835,85.7%sensitivity,76.9%specificity).Preoperatively,miR-155-5p,miR-223-3p,and miR-320a-3p were differentially expressed and targeted the forkhead box O and Hippo pathways(P<0.01).CONCLUSION Our study demonstrates,for the first time,that plasma miR-320a-3p levels can be used as a preclinical biomarker for NEC in term newborns with CHD.展开更多
基金Supported by the Natural Science Foundation of Liaoning Province,No.201602817
文摘BACKGROUND Ectopic expression of miRNAs promotes tumor development and progression.miRNA(miR)-320a is downregulated in many cancers,including gastric cancer(GC).However,the mechanism underlying its downregulation and the role of miR-320a in GC are unknown.AIM To determine expression and biological functions of miR-320a in GC and investigate the underlying molecular mechanisms.METHODS Quantitative real-time polymerase chain reaction(PCR)was used to determine expression of miR-320a in GC cell lines and tissues.TargetScanHuman7.1,miRDB,and microRNA.org were used to predict the possible targets of miR-320a,and a dual luciferase assay was used to confirm the findings.Western blotting was used to detect the protein levels of pre-B-cell leukemia homeobox 3(PBX3)in GC cells and tissue samples.Cell Counting Kit-8 proliferation,Transwell,wound healing,and apoptosis assays were performed to analyze the biological functions of miR-320a in GC cells.Methylation-specific PCR was used to analyze the methylation level of the miR-320a promoter CpG islands.5-Aza-2’-deoxycytidine(5-Aza-CdR)and trichostatin A(TSA)were used to treat GC cells.RESULTS miR-320a expression was lower in GC cell lines and tissues than in the normal gastric mucosa cell line GES-1 and matched adjacent normal tissues.miR-320a overexpression suppressed GC cell proliferation,invasion and migration,and induced apoptosis.PBX3 was a target of miR-320a in GC.The methylation level of the miR-320a promoter CpG islands was elevated and this was partly reversed by 5-Aza-CdR and TSA.CONCLUSION miR-320a acts as a tumor suppressor and inhibits malignant behavior of GC cells,partly by targeting PBX3.DNA methylation is an important mechanism associated with low expression of miR-320a.
文摘We rechecked the original data of Figure 3,Part.B,and found that 0 h group in the BGC-823 cell wound scratch assay was misapplied.Therefore,we are writing to apply for the modification of Figure 3,Part.B.
基金Supported by The Russian Science Foundation,No.19-75-20076.
文摘BACKGROUND Necrotizing enterocolitis(NEC)remains a prominent gastrointestinal emergency among infants,particularly term infants with congenital heart defects(CHD)being at high risk.The molecular processes that contribute to NEC have yet to be completely understood.The high mortality rates necessitate an active search for noninvasive biomarkers that can aid in the preclinical diagnosis and prognosis of NEC.MicroRNAs(miRs),which are involved in many biological processes in both health and disease,have been discovered to play an important role in regulating inflammation and immune responses via various signaling pathways.AIM To determine the plasma levels of miR-155,miR-221,miR-223,miR-320a,miR-451a as potential NEC biomarkers in term newborns with CHD.METHODS This prospective cohort study included twenty-tree term newborns with CHD who underwent cardiac surgery on the median day of life(DOL)=7.Nine of them developed NEC(Bell’s stage IIA and IIIA)within 1 week of cardiac surgery(NEC newborns).Blood samples were collected before(median DOL=5)and following(median DOL=13)cardiac surgery.Levels of plasma miR-155-5p,miR-221-3p,miR-223-3p,miR-320a-3p,and miR-451a were determined using real-time polymerase chain reaction.The functional analysis was executed using the DIANA-miRPath v4.0.RESULTS Preoperatively,NEC newborns had significantly lower plasma levels of miR-155(2.70-fold,P=0.020),miR-223(2.42-fold,P=0.030),and miR-320a(3.62-fold,P=0.006)than newborns without NEC.Postoperatively,miR-451a levels differed significantly between the newborn groups,showing a 4.70-fold decrease(P=0.014)in expression when clinical NEC symptoms appeared.According to receiver operating characteristic analysis,miR-320a was found to be the most effective predictive biomarker for NEC[area under the curve(AUC)=0.835,63%sensitivity,100%specificity],while miR-451a was identified as a NEC biomarker(AUC=0.835,85.7%sensitivity,76.9%specificity).Preoperatively,miR-155-5p,miR-223-3p,and miR-320a-3p were differentially expressed and targeted the forkhead box O and Hippo pathways(P<0.01).CONCLUSION Our study demonstrates,for the first time,that plasma miR-320a-3p levels can be used as a preclinical biomarker for NEC in term newborns with CHD.
