| Doxorubicin is a kind of broad-spectrum chemotherapy drug,which is widely used in breast cancer,blood system tumor,digestive tract tumor and other malignant tumors.However,while doxorubicin can inhibit tumor cells,it can also inhibit normal tissue cells,because it does not specifically act on tumor cells,that is the toxic and side effects of doxorubicin,and the cardiac toxicity is very common and frequently studied,especially the toxicity on cardiomyocytes.Most studies focus on the cardiomyocytes other than non-myocyte such as vascular endothelial cell.In view of the special structure and function of heart tissue,especially the important role of microvascular homeostasis in myocardial cells and tissues,we try to explain the cardiotoxicity of doxorubicin by studying the effect of doxorubicin on vascular homeostasis.Vascular endothelial growth factor(VEGFA)plays a very important role in maintaining the structure and function of blood vessels,and it has been reported that doxorubicin can inhibit the expression of VEGFA.In addition,in the pre-experiment,we used gene chip to screen high expression mir-526b-3p,so we want to explore the role and mechanism of mir-526b-3p and VEGFA in doxorubicin-induced cardiotoxicity.Part 1:the role of mir-526b-3p in DOX-induced cardiotoxicity and microvessels hurtObjective:to explore whether mir-526b-3p is involved in DOX-induced cardiotoxicity and microvessels' damage.Method:1?10 C57BL/6 male mouse,divided into the following groups according to the protocol:control group,DOX group.As for DOX group,Single-shot intraperitoneal injection of DOX,25mg/kg.As for control group,give the saline of the same volume.2weeks later,use echocardiography to detect the FS/EF;use immunohistochemistry to test the CD31/CD34 of the mouse heart;use microarry to analysis the expression of different miRNAs.2.40 C57BL/6 male mouse,divided Into the following groups according to the protocol:control,DOX,DOX+rAAV-GFP,DOX+rAAV-miR-526b-3p,DOX+rAAV-miR-526b-3p+TuDs,DOX+rAAV-miR-526b-3p-mut.Nothing for control;only DOX for DOX group;for DOX+rAAV-GFP group,treatment with DOX and rAAV-GFP;for DOX+rAAV-miR-526b-3p group,treatment with DOX and rAAV-miR-526b-3p;for DOX+rAAV-miR-526b-3p+TuDs group,treatment with DOX and rAAV-miR-526b-3p+TuDs;for DOX+rAAV-miR-526b-3p-mut group,treatment with DOX and rAAV-miR-526b-3p-mut.rAAV-miR-526b-3p+TuDs is a long-acting inhibitor of miR-526b-3p.rAAV-miR-526b-3p-mut is mutational of miR-526b-3p.all groups but not control group treatment with DOX 25mg/kg,ip.2weeks later,use qrt-PCR to test the expression of miR-526b-3p,use immunohistochemistry to test the CD31/CD34 of the mouse heart to value microvascular quantity and density,use echocardiography to detect the FS/EF in the control,DOX,DOX+rAAV-GFP and DOX+rAAV-miR-526b-3p groups to value the heart function.Results:1.The results of RT-qPCR and immunohistochemical staining showed that the expression level of mir-526b-3p in the heart tissue of doxorubicin treated mice was significantly increased(doxorubicin group was higher than control group:4.94±0.49 vs 1.00±0.16,P<0.01),while the expression levels of CD31 and CD34 were decreased(as for CD31:doxorubicin group was lower than control group,0.65±0.09 vs 1.00±0.16,P<0.01;as for CD34:0.63±0.09vs 1.00±0.10,P<0.01).2.Overexpression and interference of mir-526b-3p were used to detect the regulatory effect of mir-526b-3p on cardiac microvessel' s quantity and density in doxorubicin treated mice.The results were as follows:the relative expression levels of mir-526b-3p in control group,DOX group,DOX+rAAV-GFP group,DOX+rAAV-miR-526b-3p group,DOX+rAAV-MiR-526b-3p-TuDs group and DOX+rAAV-miR-526b-3p-mut group were 1.00±0.11,4.26±0.53,4.54±0.11,9.72±1.39,1.26±0.19,4.08±0.68,respectively.Compared with DOX+rAAV-GFP,mir-526b-3p in DOX+rAAV-miR-526b-3P group was significantly higher,4.54±0.11 vs 9.72±1.39;Compared with DOX+rAAV-miR-526b-3P group,miR-526b-3p decreased in DOX+rAAV-miR-526b-3p+TuDs group,9.72±1.39 vs 1.26±0.19,p<0.01;there was no significant difference between DOX group and DOX+rAAV-miR-526b-3p-mut group,4.26±0.53 vs 4.08±0.68,p>0.05;the relative expression levels of CD31 in the above six groups were 1.00±0.15,0.69±0.10,0.73±0.11,0.45±0.07,0.85±0.10,0.59±0.06,respectively,with similar results.Compared with DOX+rAAV-GFP,CD31in DOX+rAAV-miR-526b-3P group was significantly lower;0.73±0.11 vs 0.45±0.07;Compared with DOX+rAAV-miR-526b-3P group,CD31 increased in DOX+rAAV-miR-526b-3p+TuDs group,0.45±0.07vs 0.85±0.10,p<0.01;there was no significant difference between DOX group and DOX+rAAV-miR-526b-3p-mut group,0.69±0.10 Vs 0.59±0.06,p>0.05;the relative expression levels of CD34 in the above six groups were 1.00±0.14,0.70±0.08,0.56±0.07,0.41±0.43,0.82±0.12,0.59±0.07,respectively,with the similar results of CD31.It indicated that DOX induced high expression of miR-526b-3p,while high expression of miR-526b-3p inhibited microvessel' s quantity and density in mouse heart tissue.3.In the model of high expression of mir-526b-3p,the values of FS and LVEF in mouse heart were detected by ultrasound.The results were as follows:the left ventricular ejection fraction of control group,DOX group,DOX+rAAV-GFP group and DOX+rAAV-miR-526b-3p group were(78.03±14.84)%,(57.12±14.58)%,(56.06±18.86)%,(20.18±4.25)%,respectively.Compared with control group,the left ventricular ejection fraction of DOX group was significantly reduced,(78.03±14.84)%vs(57.12±14.58)%;Compared with DOX+rAAV-GFP group,DOX+rAAV-miR-526b-3p group decreased significantly,(56.06±18.86)%vs(20.18±4.25)%,P<0.01;the shortening rate of left ventricular short axis in the above four groups was(54.27±5.48)%,(28.75±3.83)%,(26.65±4.25)%,(11.80±12.67)%,respectively.Compared with the control group,the DOX group decreased significantly,(54.27±5.48)%vs(28.75±3.83)%,P<0.01:compared with the DOX+rAAV-GFP group,the DOX+rAAV-miR-526b-3p group decreased significantly,(26.65±4.25)%vs(11.80±2.67)%,P<0.01.Conclution:DOX induced miR-526b-3p high expression and do harm onmouce's heart function and microvelsses'quantity and density.And high expression of miR-526b-3p exacerbate DOX's side effects.Part 2:the role of high expression of mir-526b-3p in the function of HUVECObjective:to explore whether high expression of mir-526b-3p impairs thefunction of HUVEC including proliferation,apoptosis,tube forming ability and tube migration ability.Method:cells transfection whith mir-526b-3p mimic and inhibitor,NCmimics,NCinhibitor respectively for 36h then treated with DOX(5?M)for 12h,and then test the expression of mir-526b-3p to make sure of the transfection effection,then Edu test,flow cytometry,tubue formation test and Transwell test were used to detect the proliferation activity,apoptosis level,angiogenesis ability and cell migration ability of HUVECs.The related miRNA dose is 5?L.Results:?The transfection effects:The relative expression levels of mir-526b-3p in control group,DOX induced group,DOX+NCmimic,DOX+miR-526b-3p mimic group,DOX+NC inhibitor group and DOX+miR-526b-3p-inhibitor group were 1.00±0.11,5.61±0.85,5.13±0.78,10.53±1.20,4.77±0.53,1.82±0.26,respectively.Compared with control group,DOX inhibited the expression of mir-526b-3p,1.00±0.11vs5.61±0.85,P<0.01;compared with Ncmimic group,the expression of mir-526b-3p in mir-526b-3p mimic group increased,5.13±0.78vs10.53±1.20,P<0.01;compared with NC inhibitor group,the expression of mir-526b-3p inhibitor group decreased,4.77±0.53vs1.82±0.26,P<0.01.?proliferation:the proliferation levels of mir-526b-3p in control group,DOX induced group,DOX+NCmimic,DOX+miR-526b-3p mimic group,DOX+NC inhibitor group and DOX+miR-526b-3p-inhibitor group were 62.00±6.24,25.67±4.73,29.33±3.51,12.33±3.51,26.87±5.06,54.33±3.51.Compared with control group,DOX inhibited the proliferation activity of umbilical vein endothelial cells,62.00±6.24vs25.67±4.73,P<0.01;compared with NC MIMC group,the proliferation activity of mir-526b-3p MIMC group decreased,29.33±3.51 vs12.33±3.51,P<0.01;compared with NC inhibitor group,the proliferation activity of mir-526b-3p inhibitor group increased,26.87±5.06vs54.33±3.51,P<0.01.?Apoptosis:the relative apoptosis levels of mir-526b-3p in control group,DOX induced group,DOX+NCmimic,DOX+miR-526b-3p mimic group,DOX+NC inhibitor group and DOX+miR-526b-3p-inhibitor group were 1.03±0.06,2.95±0.19,3.14±0.26,4.95±0.30,2.95±0.25,1.50±0.42.compared with control group,the apoptosis level of DOX group increased,11.03±0.06vs2.95±0.19;compared with NC MIMC group,the apoptosis level of mir-526b-3p MIMC group increased,3.14±0.26vs4.95±0.30,P<0.01;compared with NC inhibitor group,the apoptosis level of mir-526b-3p inhibitor group decreased,2.95±0.25vs1.50±0.42,P<0.01.?Tube forming ability:the relative tube forming ability levels of mir-526b-3p in control group,DOX induced group,DOX+NCmimic,DOX+miR-526b-3p mimic group,DOX+NC inhibitor group and DOX+miR-526b-3p-inhibitor group were0.99±0.01,0.25±0.11,0.28±0.11,0.10±0.02,0.31±0.06,0.92±0.02.Compared with the control group,the number of DOX tubes decreased significantly,0.99±0.01vs 0.25±0.11,P<0.01;compared with the NC mimic group,the number of mir-526b-3p tubes decreased significantly;0.28±0.1vs 0.10±0.02,P<0.01;compared with the NC inhibitor group,the number of mir-526b-3p tubes increased significantly,0.31±0.06 vs 0.92±0.02,P<0.01.?migration ability:the relative migration ability levels of mir-526b-3p in control group,DOX induced group,DOX+NCmimic,DOX+miR-526b-3p mimic group,DOX+NC inhibitor group and DOX+miR-526b-3p-inhibitor group were 0.99±0.01,0.32±0.04,0.35±0.03,0.09±0.03,0.29±0.04,0.89±0.04.Compared with the control group,the migration ability of DOX group decreased significantly,0.99±0.01vs 0.32±0.04,P<0.01;compared with the NC mimic group,the migration ability of the miR-526b-3p mimic group decreased significantly,0.35±0.03 vs 09±0.03,P<0.01;compared with the NC inhibitor group,the migration ability of the miR-526b-3p inhibitor increased significantly,0.29±0.04 vs 0.89±0.04,p<0.01.Conclution:high expression of mir-526b-3p impairs the function of HUVEC including proliferation,apoptosis,tube forming ability and tube forming ability.Part3.The role of VEGFA in the high expression of miR-526b-3p on the function of HUVECObjective:to explore whether VEGFA alleviates the impairment of high expression of miR-526b-3p on the function of HUVEC.Method:First,HUVEC was diveded into two groups,control and DOX group.DOX group treatment with DOX(5?M)while the control group treated with noting,then test the expression of VEGFAmRNA.Cell divided into the followinggroups,DOX+NCmimics,DOX+miR-526b-3pmimics,DOX+pcDNA,DOX+pcDNA-VEGFA and DOX+miR-526b-3p mimics+pcDNA-VEGFA.cells transfection with NC mimics or miR-526b-3p mimics or pcDNA3.1 vector or pcDNA3.1-VEGFA vector for 36h.pcDNA3.1-VEGFA vector is vector of high expression of VEGFA.Then treated with DOX(5?M)for anther 12h,then Edu test,flowcytometry,tubue formation test and Transwell test were used to detect the proliferation activity,apoptosis level,angiogenesis ability and cell migration ability of HUVECs.The dose of pcDNA is 2 ? g,related miRNA dose is 5?L.Results:?The results of 2-??C analysis were as follows:compared with control group,the VEGFA miRNA of DOX group decreased significantly,1.00±0.13vs.0.38±0.04,*p<0.01;?Proliferative activity after the introduction of VEGFA:the Proliferative activity in DOX+NC mimics group,DOX+miR-526b-3p mimics group,DOX+pcDNA group,DOX+pcDNA-VEGF group ? DOX+miR-526b-3p mimics+pcDNA-VEGFA group were 30.30±2.36,14.17±3.01,30.83±3.55,66.00±4.58,23.17±3.01.Compared with the DOX+NC mimics group,the relative activity of cells in the DOX+miR-526b-3p mimics group decresed,30.30±2.36vs14.17±3.01,p<0.01;Compared with the pcDNA group,the relative activity of cells in the pcDNA-VEGFA group was significantly increased,30.83±3.55vs 66.00±4.58,P<0.01;compared with the miR-526b-3p mimics group,the relative activity of cells in the miR-526b-3p mimics+pcDNA-VEGFA group was significantly increased,14.17±3.01vs 23.17±3.01,P<0.01.?Apoptosis after the introduction of VEGFA:the relative Proliferative activity in DOX+NC mimics group,DOX+miR-526b-3p mimics group,DOX+pcDNA group,DOX+pcDNA-VEGF group ? DOX+miR-526b-3p mimics+pcDNA-VEGFA group were0.98±0.02,2.19±0.18,1.01±0.02,0.38±0.06,1.12±0.13.Compared with the DOX+NC mimics group,the relative apoptosis in the DOX+miR-526b-3p mimics group incresed,0.98±0.02vs2.19±0.18,P<0.01;compared with the pcDNA group,apoptosis in the pcDNA-VEGFA group was significantly reduced,1.01±0.02 vs 0.38±0.06,P<0.01;compared with the miR-526b-3p mimics group,apoptosis in the miR-526b-3p mimics+pcDNA-VEGFA group was significantly reduced,2.19±0.18vs 1.12±0.13,P<0.01.?The tube-forming ability of cells after the introduction of VEGFA:the relative tube-forming activity in DOX+NC mimics group,DOX+miR-526b-3p mimics group,DOX+pcDNA group,DOX+pcDNA-VEGF group ? DOX+miR-526b-3p mimics+pcDNA-VEGFA group were 0.99±0.01,0.30±0.04,1.01±0.02,2.62±0.13,1.18±0.20.Compared with the DOX+NC mimics group,the relative activity of cells in the DOX+miR-526b-3p mimics group decreased,0.99±0.01vs0.30±0.04,P<0.01.compared with the pcDNA group,the tube-forming ability of pcDNA-VEGFA was significantly increased,0.01±0.02vs 2.62±0.13,P<0.01;compared with the miR-526b-3p mimics group,the relative activity of the miR-526b-3p mimics+pcDNA-VEGFA group was significantly increased,0.30±0.04vs 1.18±0.20,P<0.01.?Cell migration ability after the introduction of VEGFA:the relative Cell migration activity in DOX+NC mimics group,DOX+miR-526b-3p mimics group,DOX+pcDNA group,DOX+pcDNA-VEGF group,DOX+miR-526b-3p mimics+pcDNA-VEGFA group were 0.99±0.01,0.35±0.02,0.10±0.01,2.05±0.08,0.84±0.05.Compared with the DOX+NC mimics group,the relative activity of cells in the DOX+miR-526b-3p mimics group decreased,0.99±0.01vs 0.35±0.02,P<0.01.Compared with the pcDNA group,the migration ability of the pcDNA-VEGFA group increased,0.10±0.01vs2.05±0.08,P<0.01;compared with the miR-526b-3p mimics group,the relative activity of the miR-526b-3p mimics+pcDNA-VEGFA group increased significantly,0.35±0.02 vs0.84±0.05,P<0.01.Conclution:Re-introduction of VEGFA alleviates the impairment of highexpression of miR-526b-3p on the function of HUVEC.Part4.Mir-526b-3p negatively regulates VEGFA and the mechanismObejective:to explore the mechanism of Mir-526b-3p and VEGFA interaction.Method:1.Cells transfection with NC mimics,miR-526b-3p mimics,NC inhibitor,miR-526b-3p inhibitor respectively and diveded into following groups DOX+NC mimics,DOX+miR-526b-3p mimics,DOX+NC inhibitor,DOX+miR-526b-3p inhibitor according to the transfection materials.Transfection for 36h,then treated with DOX(5?M)for another 12h.Dose of related miRNA is 5 ? L.Use qrt-PCRto test VEGFAmRNA in order to estimate whether miR-526b-3p regulate VEGFA or not.2.prepare the vector pcDNA-EGFP-VEGFA which contain VEGFA3'UTR sequence.Then cells were diveded into following groups,NC mimics+pcDNA3.1-EGFP-VEGFA,miR-526b-3p mimics+ pcDNA3.1-EGFP-VEGFA,NC inhibitor+pcDNA3.1-EGFP-VEGFA,miR-526b-3p inhibitor+pcDNA3.1-EGFP-VEGFA.The different groups meaned different transfection prodcuts according to the protocol.Cells transfection for 24h the treated with DOX(5?M)for another 12h.Related dose of pcDNA-EGFP-VEGFA vector was 0.5?g,the dose of related miR was 0.25uL.Then test luciferase activity to assess the interaction between miR-526b-3p and VEGFA3'UTR.3.prepare the vector pGL3-VEGFA+PRL-SV40 which contain VEGFA prometor.Then cells were diveded into following groups,pGL3-VEGFA+PRL-SV40+NC,mimics,pGL3-VEGFA+PRL-SV40+miR-526b-3p mimics,pGL3-VEGFA+PRL-SV40+NC inhibitor,pGL3-VEGFA+PRL-SV40+miR-526b-3p inhibitor.the different groups meaned different transfection prodcuts according to the protocol.Cells transfection for 24h then treated with DOX(5?M)for another 24h.the dose of related pGL3-VEGFA+PRL-SV40 vector was 0.5?g,the dose of related miR was 0.25uL.Then test luciferase activity to assess the interaction between miR-526b-3p and VEGFA prometor.4.Use JASPARS Web and starbase2.0 software to search some valuable information,such as binding site and binding sequence.5.prepare the related si-NC,si-STAT3#1,si-STAT3#2,pcDNA3.1 and pcDNA3.1/STAT3.si-NC is negetive contol of si-STAT3,si-STAT3#1 and si-STAT3#2 were different si-STAT3,pcDNA3.1/STAT3 was vector which high expression of STAT3.Then cells were diveded into following groups,si-NC,si-STAT3#1,si-STAT3#2,pcDNA3.1,pcDNA3.1/STAT3.the different groups meaned different transfection materials according to the protocol.Dose of related siRNA is 100nM,10?L,related pcDNA3.1 for 4 ?g.Cells transfection for 36h then treated with DOX(5?M)for another 12h,then use qrt-PCRto test the expression of VEGFAmRNA in order to assess whether STAT3 regulate VEGFA or not.6.use CHIP to assess the bindingsite of STAT3 and VEGFA.7.use Luciferase reporter gene to estimate the interaction between STAT3 and VEGFA-BS1.Construction plasmid carrying VEGFA-BS1WT/MUT named PGL3-BS1 WT/MUT,and construction plasmid with high or no expression of STAT3,prepare siRNA such as si-STAT3#1,si-STAT3#2,si-NC to Interfer expression of STAT3.Then cells divided into following groups,PGL3-BS1WT/MUT+si-NC,PGL3-BS1 WT/MUT+si-STAT3#1,PGL3-BS 1 WT/MUT+si-STAT3#2,PGL3-BS 1 WT/MUT+pcD NA3.1,PGL3-BS1WT/MUT+pcDNA3.1/STAT3 group.The different groups meaned different transfection materials according to the protocol.Cells transfection for 24h then treated with DOX(5?M)for another 24h,test the luciferase activity to value the interaction between STAT3 and VEGFA-BS1.Related dose of plasmid was 0.5?g,siRNA 100nM,10?L.8.Prepare the plasmid carrying wild type and mutational type of STAT3 3'UTR named psiCHECK2-STAT3 WTor MUT respectivly.And prepare the NC mimics,miR-526b-3p mimics,NC inhibitor,miR-526b-3p inhibitor.Then cells transefection with the designated marterials in different groups,cells were divided into following groups,psiCHECK2-STAT3 WT/MUT+NC mimics,psiCHECK2-STAT3 WT/MUT+miR-526b-3p mimics,psiCHECK2-STAT3 WT/MUT+NC inhibitor,psiCHECK2-STAT3 WT/MUT+miR-526b-3p inhibitor.Cells transfection for 24h,then treated with DOX(5?M)for another 24h,then test the luciferase activity.Dose of related miRNA is 5 ?L,dose of plasmid was 0.5?g.Results:1.mir-526b-3p regulate VEGFA?Negative regulation:compared with NC mimics group,the relative expression of VEGFA in mir-526b-3p mimics group was inhibited,1.00±0.15vs 0.33±0.03,P<0.01;compared with NC inhibitor group,the relative expression of VEGFA in mir-526b-3p inhibitor group was increased,1.00±0.13vs 3.41±0.58,P<0.01.?There was no binding effect between mir-526b-3p and VEGFA 3'UTR.The EGFP luciferase activity of NC mics,mir-526b-3p mics,NC inhibitor and mir-526b-3p inhibitor was 1.00±0.11,1.07±0.15,1.00±0.15,0.96±0.13,respectively.There was no significant difference between the two groups(P>0.05).?Mir-526b-3p inhibited the promoter activity of VEGFA:Luciferase Report test found that compared with NC mimics group,the promoter activity of VEGFA in mir-526b-3p mimics group was inhibited,1.00±0.13vs.0.30±0.04,P<0.01;compared with NC inhibitor group,the promoter activity of VEGFA in mir-526b-3p inhibitor group was increased,1.00±0.10vs 2.4710.38,P<0.01.2.According to Jaspar analysis,VEGFA promoter and STAT3 have two effective binding sites(BS1,BS2).Use Starbase2.0soft ware to definite the binding supuence between STAT3 and miR-526b-3p.3.STAT3 positively regulated VEGFAmRNAcompared with Si-nc group,the mRNA level of VEGFA in si-stat3#1 group and si-stat3#2 group was significantly lower,1.000±0.17 vs 0.34±0.05/0.30±0.04,P<0.01.Compared withpcDNA3.1 group,the mRNA level of VEGFA in pcdna3.1/stat3 group was significantly higher,1.00±0.18 vs 3.32±0.42,P<0.01.4.The binding of STAT3 to VEGFA in BS1 was confirmed by chromatin immunoprecipitation assay.In BS1 binding site,IgG vs STAT3:0.93±0.10vs 28.29±4.7,P<0.01.In BS2 binding site,IgG vs STAT3:0.96±0.11 vs 1.23±0.20,P>0.05.5.Luciferase assay showed that STAT3 binds to VEGFA promoter at prediction site 1(BS1)In BS1 wild type group,compared with Si NC group,luciferase activity of Si STAT3#1 group and Si STAT3#2 group was inhibited,1.00±0.15vs 0.29±0.04/0.33±0.05,P<0.01;compared with pcDNA3.1 group,luciferase activity of pcDNA3.1/stat3 group was increased,1.00±0.13vs 2.52±0.38,P<0.01.There was no significant difference in BS1 mutation group.Compared with Si NC group,luciferase activity of Si STAT3#1 group and Si STAT3#2 group was no change,1.00±0.16vs1.04±0.15vs 0.88±0.13;compared with pcDNA3.1 group,luciferase activity of pcDN A3.1/stat3 group was no change,1.00±0.11 vs 1.00±0.13.6.To verify the negtively regulation of mir-526b-3p on STAT3to establish STAT3 wild type and STAT3 mutant luciferase reporter gene,in stat3-WT,compared with NC MICs group,the luciferase activity of mir-526b-3p MICs group decreased,1.00±0.13 vs 0.16±0.05,P<0.01;compared with NC inhibitor group,mir-526b-3p inhibitor group,luciferase activity increased,1.00±0.15 vs 2.39±0.38,P<0.01.In stat3-MUT group,the activities of luciferase in NC MICs group,mir-526b-3p MICs group,NC inhibitor group and mir-526b-3p inhibitor group remained unchanged,and the relative activities of stat3-mut luciferase in the four groups were 1.00±0.14,1.01±0.11,0.92±0.14,0.96±0.11,respectively,with no significant difference(P>0.05).Conclusion:mir-526b-3p positively regulate STAT3,and negtively regulate VEGFA,STAT3 positively regulate VEGFA.So,mir-526b-3p/STAT3/VEGFA may be a pathway involved in DOX-induced microvascular injury and cardiac dysfunction. |
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