HDAC11 mediates the ubiquitin-dependent degradation of p53 and inhibits the anti-leukemia effect of PD0166285.

Cytarabine-resistant acute myeloid leukemia (AML) is a common phenomenon, necessitating the search for new chemotherapeutics. WEE1 participates in cell cycle checkpoint signaling and inhibitors targeting WEE1 (WEE1i) constitute a potential novel strategy for AML treatment. HDAC (histone deacetylase) inhibitors have been shown to enhance the anti-tumor effects of WEE1i but molecular mechanisms of HDAC remain poorly characterized.

MiR-454-3p promotes apoptosis and autophagy of AML cells by targeting ZEB2 and regulating AKT/mTOR pathway.

Background: miR-454-3p is considered to have a crucial role in cancer progression, but the potential involvement in acute myeloid leukemia (AML) remains unclear.

Methods: Expression of miR-454-3p and ZEB2 mRNA and protein were quantified in AML cell lines. Cells were transfected with miR-454-3p inhibitor or mimic and cell growth was assessed by colony formation and CCK-8 assays and the cell cycle, apoptosis and autophagy were investigated by Western blotting, flow cytometry, immunofluorescence and 3-methyladenine (3-MA) treatment.

DNMT3A R882H mutation promotes acute leukemic cell survival by regulating glycolysis through the NRF2/NQO1 axis.

Background: Studies have confirmed that acute myeloid leukemia (AML) cells with DNA methyltransferase 3A Arg882His (DNMT3A R882H) mutation show an increased proliferation capability. However, the associated mechanism is still unclear. Glycolysis is involved in regulating malignant proliferation of cancer cell.

DNMT3A R882H mutation drives daunorubicin resistance in acute myeloid leukemia via regulating NRF2/NQO1 pathway.

Background: DNA methyltransferase 3A (DNMT3A) often mutate on arginine 882 (DNMT3A) in acute myeloid leukemia (AML). AML patients with DNMT3A R882 mutation are usually resistant to daunorubicin treatment; however, the associated mechanism is still unclear. Therefore, it is urgent to investigate daunorubicin resistance in AML patients with DNMT3A R882 mutant.

miRNA-222-3p enhances the proliferation and suppresses the apoptosis of acute myeloid leukemia cells by targeting Axin2 and modulating the Wnt/β-catenin pathway.

MicroRNA (miRNA)-222-3p is overexpressed in numerous tumors, where it acts as an oncogene. Although miRNA-222 is highly expressed in acute myeloid leukemia (AML), its functions and the mechanisms underlying these functions have not yet been fully elucidated. This study aimed to investigate the regulatory roles of miRNA-222-3p in AML and the molecular mechanisms underlying these roles.

RIP1-dependent Apoptosis and Differentiation Regulated by Skp2 and Akt/GSK3β in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by variations in cytogenetics and molecular abnormalities, which result in variable response to therapy. Receptor-interacting serine/threonine kinase 1 (RIP1)-mediated necroptosis has been reported to have a potential role in the treatment of AML. We obtained Skp2 and RIP1 are significantly overexpressed in AML samples using original published data, and identified that Skp2-depletion in AML cells significantly suppressed RIP1.

MiRNA-301b-3p induces proliferation and inhibits apoptosis in AML cells by targeting FOXF2 and regulating Wnt/β-catenin axis.

Background: MiRNA-301b-3p functions as an oncomiRNA or tumor suppressor, and has been reported in various cancer types, including pancreatic, colorectal, oral, hepatocellular and lung cancers. Although the expression of miRNA-301b-3p is upregulated in acute myeloid leukemia (AML), its biological function and precise mechanisms remain unclarified. This study explores the roles of miRNA-301b-3p in AML, with the aim of ascertaining its regulatory action on Wnt/β-catenin axis by targeting Forkhead box F2 (FOXF2).

ZFP91 promotes cell proliferation and inhibits cell apoptosis in AML via inhibiting the proteasome-dependent degradation of RIP1.

Acute myeloid leukemia (AML) is a quickly progressive and devastated hematological malignancy with large rate of relapse and the appearance of chemotherapy resistance. Therefore, the identification of new therapeutic targets is urgent. ZFP91 is a hidden oncogene.

Skp2 promotes APL progression through the stabilization of oncoprotein PML-RARα and the inhibition of JunB expression.

Aims: To investigate the role of Skp2 and JunB on acute promyelocytic leukemia (APL) progression and the related mechanism.

Materials And Methods: The expression of Skp2 in NB4 cell line was depleted to explore its effect on proliferation and differentiation both in vitro and in vivo assays. Western blot and quantitative RT-PCR analysis were performed to explore Skp2-regulated downstream target genes.

[lncRNA CRNDE promotes proliferation and inhibits apoptosis of U937 cells by downregulating miR-136-5p and upregulating MCM5].

Objective To investigate the effect of lncRNA CRNDE on proliferation, apoptosis, and cell cycle of U937 cells and its mechanism. Methods The expression level of CRNDE in bone marrow cells of AML patients was analyzed by GEPIA database; the mRNA expression levels of miR-136-5p, CRNDE, and minichromosome maintenance 5(MCM5) in AML cell lines were detected by quantitative real-time PCR (qRT-PCR). The lentiviral vector with CRNDE knocked down was constructed and transfected into U937 cells which were randomized into CRNDE knockdown group (sh-CRNDE group) and negative control group (sh-NC group); miR-136-5p mimic and miR-136-5p inhibitor were transfected respectively to overexpress and knock down miR-136-5p in U937 cells which were randomized into miR-136-5p-mimic group, NC-mimic group, miR-136-5p-inhibitor group, and NC-inhibitor group.

CRNDE enhances the expression of MCM5 and proliferation in acute myeloid leukemia KG-1a cells by sponging miR-136-5p.

The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene has been considered to be crucial in tumor malignancy. Although CRNDE is highly expressed in acute myeloid leukemia (AML), its mechanism of action remains unknown. In this study, GEPIA and qRT-PCR were performed to confirm the expression of CRNDE in AML samples and cell lines, respectively.

Application of a Simple Microfluidic Chip Analysis Technology to Evaluate the Inhibitory Role of Protocatechuic Acid on Shear-Induced Platelet Aggregation.

This study aimed to develop a simple microfluidic chip analysis technology to study the inhibitory effect of protocatechuic acid on shear-induced platelet aggregation. The microfluidic chip designed in this study simulates 80% fixed narrow microchannels. This microchannel narrow model uses the finite element analysis module of the three-dimensional modeling software solidwork to analyze fluid dynamic behavior.

[NLS-RARα transports into the nucleus by binding to importin α1/β2(KPNA2/KPNB1) and inhibits the differentiation of U937 cells].

Objective To investigate the inhibitory effect of abnormal nuclear localization of the nuclear localization signal-retinoic acid receptor α (NLS-RARα) on cell differentiation and its mechanism of nuclear transport. Methods Over-expression of HA-NLS-RARα and empty vector in HEK293T cells and U937 cells were achieved through a lentivirus vector and were assigned as NLS-RARα over-expression (NR) group and negative control (NC) group. Extracted nucleoproteins and cytosolic proteins of NC and NR groups of HEK293T cells and U937 cells were detected by Western blot analysis in order to demonstrate the localization of NLS-RARα.

TRIB3 destabilizes tumor suppressor PPARα expression through ubiquitin-mediated proteasome degradation in acute myeloid leukemia.

Aims: Tribbles homolog 3 (TRIB3) is emerging as a multifunctional oncoprotein associated with various cellular events in different tumors. However, the regulatory mechanism of TRIB3 in acute myeloid leukemia (AML) remains unknown. This study aims to investigate the molecular mechanisms and uncover the functions of TRIB3 in AML.

GSK-J4 induces cell cycle arrest and apoptosis via ER stress and the synergism between GSK-J4 and decitabine in acute myeloid leukemia KG-1a cells.

Background: GSK-J4 is the inhibitor of H3K27me3 demethylase. Recent studies demonstrated that GSK-J4 could affect the proliferation and apoptosis of a variety of cancer cells. However, the effects and underlying mechanisms of GSK-J4 on the proliferation and apoptosis of human acute myeloid leukemia (AML) KG-1a cells have not been explored thoroughly.

NLS-RARα blocks cell differentiation by inhibiting the retinoic acid signalling pathway.

A majority of acute promyelocytic leukaemia (APL) cases are characterized by the PML-RARα fusion gene. Previous studies have shown that neutrophil elastase (NE) can cleave PML-RARα and is important for the development of APL. Here, we demonstrate that one of the cleavage products of PML-RARα, NLS-RARα, can block cell differentiation by repressing the expression of the target genes within the retinoic acid signalling pathway.

Nuclear import of NLS- RARα is mediated by importin α/β.

The promyelocytic leukemia-retinoic acid receptor α (PML/RARα) is hypothesized to play a vital role in the pathogenesis of acute promyelocytic leukemia (APL). A previous study has demonstrated that PML/RARα is cleaved by neutrophil elastase (NE) in early myeloid cells, which leads to an increase in the nuclear localization signal (NLS) in RARα and in the incidence of APL. In this study, we explored the effects of NLS-RARα on acute myeloid leukemia (AML) cells and studied the mechanism of its localization.

Neutrophil elastase-mediated proteolysis of the tumor suppressor p200 CUX1 promotes cell proliferation and inhibits cell differentiation in APL.

Aims: Neutrophil elastase (NE) is a critical proteolytic enzyme that is involved in cancer. We previously reported high NE expression in peripheral blood neutrophils from acute promyelocytic leukemia (APL) patients. The present study aimed to elucidate the specific role and mechanisms of NE in APL development.

NLS-RARα contributes to differentiation block and increased leukemogenic potential in vivo.

The fusion oncogene, promyelocytic leukemia (PML)-retinoic acid receptor-α (RARα), is crucial for acute promyelocytic leukemia (APL) pathogenesis. Previous studies have reported that PML-RARα is cleaved by neutrophil elastase (NE), an early myeloid-specific serine protease, leading to translocation of the nuclear localization signal (NLS) of the PML protein to the N-terminal of RARα. This study was designed to evaluate the value of NLS-RARα in the early diagnosis of APL.