Low expression of microRNA-340 confers adverse clinical outcome in patients with acute myeloid leukemia.

MicroRNA-340 (miR-340) was considered as a tumor suppressor by affecting cancer cell proliferation, apoptosis, invasion, and migration, and was downregulated in diverse cancers. Moreover, dysregulation of miR-340 was also found to be associated with drug resistance and predicted patients' survival in various cancers. Herein, we investigated miR-340 expression and its clinical significance in acute myeloid leukemia (AML). Real-time quantitative polymerase chain reaction was performed to detect miR-340 expression in bone marrow (BM) from 99 newly diagnosed AML patients except for acute promyelocytic leukemia (APL), 19 AML patients achieved complete remission (CR), and 29 healthy donors. BM miR-340 expression was significantly underexpressed in newly diagnosed AML patients as compared with controls (p = 0.031) and AML patients achieved CR (p = 0.025). No significant differences were observed between miR-340 expression and most of the clinicopathologic features (p > 0.05). However, low miR-340 expression was found to be associated with lower CR rate in both non-APL-AML and cytogenetically normal AML (CN-AML; p = 0.001 and 0.031, respectively), and acted as an independent risk factor for CR by logistic regression analysis (p = 0.001 and 0.021, respectively). More important, among both non-APL-AML and CN-AML, low expression of miR-340 was also associated with shorter overall survival (OS; p = 0.013 and 0.005, respectively), and was further validated by Cox regression (p = 0.031 and 0.039, respectively). Collectively, our study showed that BM miR-340 expression was downregulated in AML, and low expression of miR-340 correlated with adverse prognosis.

miR-590 promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia by inhibiting RB1.

MicroRNAs play important roles in the pathogenesis of cancers by inhibiting gene expression at posttranscriptional level. Here, we identified that miR-590 and its predicted target gene RB1 are differentially expressed in T-cell acute lymphoblastic leukaemia (T-ALL). The correlation between miR-590 and RB1 was further confirmed in 395 T-ALL patients. In T-ALL cell lines, miR-590 promoted the cell proliferation by increasing G1/S transition. Moreover, migration and invasion assay showed that miR-590 promotes the migration and invasion of T-ALL cells by increasing E-cadherin and inhibiting MMP-9. Luciferase assays confirmed that miR-590 directly binds to the 3'untranslated region of RB1, and western blotting showed that miR-590 suppresses the expression of RB1 at the protein levels. This study indicated that miR-590 inhibits RB1 and promotes proliferation and invasion of T-ALL cells. Thus, miR-590 may represent a potential therapeutic target for T-ALL intervention.

The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma.

BACKGROUND: Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human osteosarcoma cells. METHODS: The effects of ectopic miR-497 expression on the cell survival and cisplatin sensitivity in osteosarcoma cells were measured by the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression of miR-497. The effects of ectopic miR-497 expression on the expression of VEGFA, Akt and p-Akt were determined by western blot. RESULTS: Real-time quantitative PCR analysis revealed that miR-497 was significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal human osteoblasts. Up-regulation of miR-497 inhibited cell survival and enhanced the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR-497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase reporter assay and western blot confirmed that VEGFA was a direct target of miR-497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin resistance. CONCLUSION: Taken together, our results suggest that miR-497 modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway in osteosarcoma cells.

miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia.

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention.

[Significance of interplay between Rap1 and cadherin to the development of myelodysplastic syndrome].

OBJECTIVE: To explore the hematopoietic pathophysiology of myelodysplastic syndrome (MDS) at stem/progenitor cell level by analyzing the gene expression profiles associated with hematopoiesis. METHODS: The differentially expressed genes which were involved in the hematopoiesis were screened by microarray using CD34(+) cells from MDS patients firstly. RQ-PCR was then applied to validate the screened genes using CD34(+) cells from MDS-RA patients who had normal karyotype. The linkages with hematopoiesis among these validated genes were analyzed. RESULTS: Among the differentially expressed genes in CD34(+) cells of MDS-RA patients, Rap1GAP was up-regulated significantly (P < 0.01). Cadherins, which can interplay with Rap1, including N-cadherin and E-cadherin, were down-regulated significantly (P < 0.01). ß-catenin, a downstream effector of cadherins, was highly expressed in MDS-RA patients (P < 0.01). c-myc binding protein was down-regulated (P < 0.01), and c-myc promoter binding protein was up-regulated (P < 0.01). Rac1, Rac2 and Cdc42, which belong to RhoGTPases family and are associated with the cell morphology and hematopoiesis, were all expressed highly in MDS-RA patients (P < 0.01). CONCLUSION: The abnormal expression of cadherin, ß-catenin and c-myc associated genes were closely related to the dysplastic hematopoiesis of MDS. The down regulation of cadherin was associated with the positive feedback mechanism between Rap1 and cadherin. The aberrant expression of Rac1, Rac2 and Cdc42 may contribute to the morphological dysplasia of MDS.