Objective:To investigate the effects of microRNA-451 on proliferation, invasion and migration of multiple myeloma RPMI-8226 cells and its mechanism.Methods:RPMI-8226 cells cultured in vitro were divided into blank control group (untransfected), negative control (NC) group and miR-451 mimic transfected (miR-451) group. The expression of miR-451 was detected by real-time quantitative PCR (qRT-PCR), cell proliferation was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) array and clone formation experiment, cell invasion and migration were detected by Transwell, and the expressions of c-Myc, MMP-2 and MMP-9 proteins were detected by western blot. The targeting relationship between miR-451 and c-Myc was detected by double luciferase reporter gene assay. Results:Compared to the blank control group, the expression level of miR-451 was increased (2.85±0.27 vs 1.02±0.06), while the cell survival rate [(47.28±3.15)% vs (93.65±6.52)%], cloning formation rate [(15.03±1.34)% vs (28.48±2.12)%], invasive cell number (86.65±5.58 vs 135.47±9.85), migrating cell number (106.36±6.48 vs 165.28±11.05) and the expression level of c-Myc(0.35±0.03 vs 0.66±0.05), MMP-2 (0.20±0.02 vs 0.48±0.03) and MMP-9 (0.28±0.03 vs 0.59±0.06) protein were significantly decreased in the miR-451 group ( P<0.05). In the negative control group, the expression level of miR-451, cell viability, clone formation rate, invasive cell number, migrating cell number, c-Myc protein, MMP-2 protein and MMP-9 protein were 0.94±0.05, (95.16±5.04)%, (27.55±2.26)%, (128.96±8.32) and (158.65±8.76), 0.68±0.06, 0.51±0.03, 0.54±0.03, respectively. There were no significant differences between the blank control group and the NC group ( P>0.05). Double luciferase reporter gene experiment confirmed that c-Myc was a potential target gene of miR-451. Conclusion:miR-451 can inhibit the proliferation, invasion and migration of RPMI-8226 cells by targeting c-Myc.

Objective To explore the correlations of serum vascular endothelial growth factor(VEGF),matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinases-1(TIMP-1)with grading of myelofibrosis(MF)in patients with myeloproliferative neoplasms(MPN).Methods Ninety patients with Philadelphia chromosome negative(Ph-)MPN were selected as MPN group.According to the grading criteria for myelofibrosis by the World Health Organization(WHO)in 2016,MPN pa-tients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases;another 50 healthy volunteers were selected as the control group.Levels of serum VEGF,MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay,and the ratio of TIMP-1 to MMP-9(TIMP-1/MMP-9)was calculated.Spearman rank correlation test was used to analyze the correlations of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 with MF grading.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of each indicator a-lone or their combination for diagnosing MPN or distinguishing MF grading.Results Compared with the control group,the serum levels of VEGF,MMP-9 and TIMP-1 in the MPN group increased significantly(P＜0.05).Values of area under the curve(AUC)of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0,834,0.745,0.923 and 0.618 respectively;the AUC of the combined diagnosis of MPN by VEGF,MMP-9 and TIMP-1 was 0.960;when the optimal cut-off value was 0.627,the sensitivity was 85.56％,and the specificity was 92.00％.Compared with the pre-fibrosis or early fibrosis group,the serum levels of VEGF,TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly(P＜0.05).Spearman correlation analysis showed that VEGF(r=0.378,P=0.001),TIMP-1(r=0.512,P＜0.001)and TIMP-1/MMP-9(r=0.353,P=0.001)were positively correlated with the MF grading of MPN patients(P＜0.05).ROC curve analysis showed that the values of AUC of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723,0.523,0.802 and 0.708 respectively;the AUC of the combined detection of VEGF,TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838;when the optimal cut-off value was 0.530,the sensitivity was 72.22％,and the specificity was 85.19％.Conclusion Serum VEGF,TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients,and the combined detection of these indica-tors can predict the MF degree of MPN patients.

Objective:To investigate the effects of microRNA-451 on proliferation, invasion and migration of multiple myeloma RPMI-8226 cells and its mechanism.Methods:RPMI-8226 cells cultured in vitro were divided into blank control group (untransfected), negative control (NC) group and miR-451 mimic transfected (miR-451) group. The expression of miR-451 was detected by real-time quantitative PCR (qRT-PCR), cell proliferation was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) array and clone formation experiment, cell invasion and migration were detected by Transwell, and the expressions of c-Myc, MMP-2 and MMP-9 proteins were detected by western blot. The targeting relationship between miR-451 and c-Myc was detected by double luciferase reporter gene assay. Results:Compared to the blank control group, the expression level of miR-451 was increased (2.85±0.27 vs 1.02±0.06), while the cell survival rate [(47.28±3.15)% vs (93.65±6.52)%], cloning formation rate [(15.03±1.34)% vs (28.48±2.12)%], invasive cell number (86.65±5.58 vs 135.47±9.85), migrating cell number (106.36±6.48 vs 165.28±11.05) and the expression level of c-Myc(0.35±0.03 vs 0.66±0.05), MMP-2 (0.20±0.02 vs 0.48±0.03) and MMP-9 (0.28±0.03 vs 0.59±0.06) protein were significantly decreased in the miR-451 group ( P<0.05). In the negative control group, the expression level of miR-451, cell viability, clone formation rate, invasive cell number, migrating cell number, c-Myc protein, MMP-2 protein and MMP-9 protein were 0.94±0.05, (95.16±5.04)%, (27.55±2.26)%, (128.96±8.32) and (158.65±8.76), 0.68±0.06, 0.51±0.03, 0.54±0.03, respectively. There were no significant differences between the blank control group and the NC group ( P>0.05). Double luciferase reporter gene experiment confirmed that c-Myc was a potential target gene of miR-451. Conclusion:miR-451 can inhibit the proliferation, invasion and migration of RPMI-8226 cells by targeting c-Myc.

Objective To explore the correlations of serum vascular endothelial growth factor(VEGF),matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinases-1(TIMP-1)with grading of myelofibrosis(MF)in patients with myeloproliferative neoplasms(MPN).Methods Ninety patients with Philadelphia chromosome negative(Ph-)MPN were selected as MPN group.According to the grading criteria for myelofibrosis by the World Health Organization(WHO)in 2016,MPN pa-tients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases;another 50 healthy volunteers were selected as the control group.Levels of serum VEGF,MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay,and the ratio of TIMP-1 to MMP-9(TIMP-1/MMP-9)was calculated.Spearman rank correlation test was used to analyze the correlations of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 with MF grading.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of each indicator a-lone or their combination for diagnosing MPN or distinguishing MF grading.Results Compared with the control group,the serum levels of VEGF,MMP-9 and TIMP-1 in the MPN group increased significantly(P＜0.05).Values of area under the curve(AUC)of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0,834,0.745,0.923 and 0.618 respectively;the AUC of the combined diagnosis of MPN by VEGF,MMP-9 and TIMP-1 was 0.960;when the optimal cut-off value was 0.627,the sensitivity was 85.56％,and the specificity was 92.00％.Compared with the pre-fibrosis or early fibrosis group,the serum levels of VEGF,TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly(P＜0.05).Spearman correlation analysis showed that VEGF(r=0.378,P=0.001),TIMP-1(r=0.512,P＜0.001)and TIMP-1/MMP-9(r=0.353,P=0.001)were positively correlated with the MF grading of MPN patients(P＜0.05).ROC curve analysis showed that the values of AUC of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723,0.523,0.802 and 0.708 respectively;the AUC of the combined detection of VEGF,TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838;when the optimal cut-off value was 0.530,the sensitivity was 72.22％,and the specificity was 85.19％.Conclusion Serum VEGF,TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients,and the combined detection of these indica-tors can predict the MF degree of MPN patients.