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 patients 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 alone 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 indicators 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 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.