BackgroundMicroRNAs (miRNAs) function as post-transcriptional gene expression regulators. Some miRNAs, including the recently discovered miR-582–3p, have been implicated in leukemogenesis. This study aimed to reveal the biological function of miR-582–3p in acute myeloid leukemia (AML), which is one of the most frequently diagnosed hematological malignancies.MethodsThe expression of miR-582–3p was determined using quantitative real-time PCR in blood samples from leukemia patients and in cell lines. Cell proliferation and cell cycle distribution were analyzed using the CCK-8, colony formation and flow cytometry assays. The target gene of miR-582–3p was verified using a dual-luciferase reporter assay. The G2/M phase arrest-related molecule contents were measured using western blotting analysis.ResultsWe found miR-582–3p was significantly downregulated in the blood samples from leukemia patients and in the cell lines. MiR-582–3p overexpression significantly impaired cell proliferation and induced G2/M cell cycle arrest in THP-1 cells. Furthermore, cyclin B2 (CCNB2) was confirmed as a target gene of miR-582–3p and found to be negatively regulated by miR-582–3p overexpression. More importantly, CCNB2 knockdown showed suppressive effects on cell proliferation and cell cycle progression similar to those caused by miR-582–3p overexpression. The inhibitory effects of miR-582–3p overexpression on cell proliferation and cell cycle progression were abrogated by CCNB2 transfection.ConclusionThese findings indicate new functions and mechanisms for miR-582–3p in AML development. Further study could clarify if miR-582–3p and CCNB2 are potential therapeutic targets for the treatment of AML.

Acute myeloid leukemia (AML) is a prevalent class of blood disease with a high occurrence rate and relapse rate. The role of dysregulated microRNAs (miRNAs) in AML is emerging. MiR-4260 was identified to be a carcinogenic miRNA in colorectal cancer, but never has it been reported in AML. We aimed to study the function and mechanism of miR-4260 in AML. The miR-4260 level was higher in AML cell lines than the normal cell lines. Inhibition of miR-4260 hindered proliferation and increased apoptosis of AML cells. Mechanistically, long intergenic non-protein coding RNA 1128 (LINC01128) competed with nuclear receptor subfamily 3 group C member 2 (NR3C2) for miR-4260 so as to upregulate NR3C2. We identified the reduced levels of LINC01128 and NR3C2 in AML and it was suggested through rescue assays that LINC01128 repressed AML progression through regulating miR-4260/NR3C2 axis. In conclusion, we firstly uncovered that LINC01128 resisted acute myeloid leukemia through regulating miR-4260/NR3C2, providing novel clues for the treatment improvement of AML.

Background: The interaction between leukocytes and vascular endothelial cells is ubiquitous in the occurrence and development of many diseases, especially in the body's defense response. The purpose of the present study was to investigate the effect of cornu bubali (CB) on the adhesion of leukocytes to endothelial cells. Materials and methods: Human leukemic cell line (HL-60) and human umbilical vein endothelial cells (HUVECs) were used to simulate the adhesion effect between cells. After HUVECs were treated with TNF- α(15 ng/mL) combined with different dose of CB (15, 30 and 60 μmol/L) and dexamethasone (DEX, 2 μg/ml) for 24 h, HL-60 cells were added into the coculture system for another 1 h. CCK8 assay was performed to investigate cell viability of HUVECs. HL-60 cells adhesion to HUVECs was quantified using Hoechst 33342 staining. Subsequently, the levels of adhesion molecules were detected by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and ELISA, respectively. RT-qPCR and western blot were performed to assess the levels of inflammatory cytokines, chemokines and the expression of Notch signaling pathway. Results: Treatment with CB could reduce the adherence of HL-60 to HUVECs induced by TNF- in a dose-dependent manner. CB inhibited the expression of ICAM-1, VCAM-1, CD44, IL-1β, COX-2 and CCL4 in HUVECs. Western blot and RT-qPCR analysis confirmed that CB prevented TNF-α -induced over-expression of Notch receptors (Notch1 and Notch2), Notch ligands (DLL1 and Jagged1), signaling effectors (Hes1) and adhesion related proteins (NF-κB/p65, p-I B and IκBκ) in HUVECs. Conclusion: CB induces interactions between leukocytes and endothelial cells through the activation of Notch signaling pathway. These data contribute to further explain the protective effect of CB against development of inflammatory process of hemorrhage in acute leukemia.