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Objective@#To explore the expression and prognostic significance of miR-223 in patients with mantle cell lymphoma (MCL) and to investigate the possible mechanism.@*Methods@#Twenty-one newly diagnosed MCL patients with bone marrow involvement were enrolled in the present study, 20 healthy donors as normal control. The expression level of miR-223 and SOX11 mRNA was determined by RQ-PCR. CCK-8 and flow cytometer assays were used to analyze cell proliferation, cell cycle and apoptosis of the constructed miR-223 overexpressing MCL cell line, Granta519 cells. SOX11 protein expression level was determined by Western blot. The target gene of miR-223 was confirmed by dual luciferase reporter assay.@*Results@#①Of the 21 newly diagnosed MCL patients, 15 were male and 6 female, the median age was 58 (37-72) years. The expression level of miR-223 was significantly down regulated in MCL patients compared with that of healthy donors (14.7±10.5 vs 1 244.1±1 935.2, P<0.001). The lower expression of miR-223 was inversely correlated with high-risk mantle international prognostic index (P=0.001), elevated LDH (P=0.001), ECOG score ≥2 (P=0.035). ②Using the median relative expression level of miR-223 as the cutoff value, 21 MCL patients were divided into high-expression group (n=10) and low-expression group (n=11) and found that the high-expression group had a significantly superior OS (median OS: 36 vs 12 months, P=0.021). ③In vitro results showed that compared with the control group, the proliferation of miR-223 overexpressed Granta519 cells was inhibited (the most significant reduction on 96h, P<0.001), manifested by lower proportion of cells in G2/M phase (P<0.001) and increased apoptosis (P<0.001), and the expression level of SOX11 protein in Granta519 cells was significantly lower than that of the control group. ④miR-223 could inhibited the 3′ untranslated region of SOX11, and the expression level of miR-223 was significantly negatively correlated with mRNA level of SOX11 in MCL patients (r=-0.81, P<0.001).@*Conclusions@#The expression of miR-223 was repressed in MCL and was associated with poor clinical outcomes, which may be probably attributed to its direct targeting SOX11.
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Objective@#To investigate the clinical significance of expression level of thyroid hormone receptor interactors 13 (TRIP13) gene to probe its function and downstream molecular mechanism in chronic lymphocytic leukemia (CLL) .@*Methods@#Real-time quantitative PCR method was used to detect the expression levels of TRIP13 mRNA of CD19+ B lymphocytes in 30 cases of patients with CLL and 12 cases of peripheral blood hematopoietic stem cell donors (normal control group) . Lentivirus mediated shRNA was used to interference the mRNA and TRIP13 protein in CLL cells JVM-2. Scramble sequence was used as control. Methyl thiazolyl tetrazolium colorimetric assay (MTT) and flow cytometry was used to detect the cell proliferation and apoptosis in TRIP13 knocked-down and negative control JVM-2 cells.@*Results@#TRIP13 mRNA level was significantly higher in 30 cases of CLL patients (2-△Ct= 0.014 89) compared with 12 healthy donors (2-△Ct= 0.000 19) (P<0.001) . Validated TRIP13 shRNA target was achieved in JVM2 cell. Compared with the control group, down-regulation of TRIP13 expression could significantly inhibit the proliferation of JVM-2 cells and induce apoptosis. The expressions of Myc and Bcl-2 protein in JVM-2 cells decreased significantly after interference with TRIP13 (P<0.001) , and the expressions of Bax, caspase 3 and Bad protein increased significantly (P<0.001) .@*Conclusion@#TRIP13 mRNA significantly over-expressed in CLL patients CD19+ B lymphocytes. TRIP13 could influence JVM2 cell proliferation and apoptosis through proliferation- and apoptosis-related proteins.