4-Amino-2-trifluoromethyl-phenyl retinate induced differentiation of human myelodysplastic syndromes SKM-1 cell lines by up-regulating DDX23

Wang, Ke; Li, Shufang; Song, Sujing; Du, Yan; Niu, Ruowen; Qian, Xuewen; Peng, Xiaoqing; Chen, Feihu

doi:10.1016/j.biopha.2019.109736

Cited by 5 publications

(6 citation statements)

References 38 publications

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“…Cell Counting Kit-8 (CCK-8) assay. As previously reported (30), SKM-1 cells in the logarithmic phase or SKM-1 cells (5x10 3 /well) following transfection were seeded in 96-well plates and grouped as previously described. The viability of the SKM-1 cells at 24, 48 and 72 h was assessed using CCK-8 assay (cat.…”

Section: Methodsmentioning

confidence: 99%

“…Flow cytometry. The SKM-1 cells were fixed in 70% ethanol at 4˚C overnight, stained with 300 ml propidium iodide (Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.) in the dark at 37˚C for 30 min, and subsequently analyzed for cell cycle distribution using a flow cytometer (MoFloAstrios EQ, Beckman Coulter) with FlowJo V10.8.1 software (Leonard Herzenberg Laboratory, Stanford University, USA), as previously described (30).…”

Section: Methodsmentioning

confidence: 99%

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MEK/ERK and PI3K/AKT pathway inhibitors affect the transformation of myelodysplastic syndrome into acute myeloid leukemia via H3K27me3 methylases and de‑methylases

Zheng,

Chen,

Zhang

et al. 2023

Int J Oncol

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The transformation of myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) poses a significant clinical challenge. The trimethylation of H3 on lysine 27 (H3K27me3) methylase and de-methylase pathway is involved in the regulation of MDS progression. The present study investigated the functional mechanisms of the MEK/ERK and PI3K/AKT pathways in the MDS-to-AML transformation. MDS-AML mouse and SKM-1 cell models were first established and this was followed by treatment with the MEK/ERK pathway inhibitor, U0126, the PI3K/AKT pathway inhibitor, Ly294002, or their combination. H3K27me3 methylase, enhancer of zeste homolog (EZH)1, EZH2, demethylase Jumonji domain-containing protein-3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) and H3K27me3 protein levels were determined using western blot analysis. Cell viability, cycle distribution and proliferation were assessed using CCK-8, flow cytometry, EdU and colony formation assays. The ERK and AKT phosphorylation levels in clinical samples and established models were determined, and SKM-1 cell behaviors were assessed. The levels of H3K27me3 methylases and de-methylases and distal-less homeobox 5 (DLX5) were measured. The results revealed that the ERK and AKT phosphorylation levels were elevated in patients with MDS and MDS-AML, and in mouse models. Treatment with U0126, a MEK/ERK pathway inhibitor, and Ly294002, a PI3K/AKT pathway inhibitor, effectively suppressed ERK and AKT phosphorylation in mice with MDS-AML. It was observed that mice with MDS treated with U0126/Ly294002 exhibited reduced transformation to AML, delayed disease transformation and increased survival rates. Treatment of the SKM-1 cells with U0126/Ly294002 led to a decrease in cell viability and proliferation, and to an increase in cell cycle arrest by suppressing ERK/PI3K phosphorylation. Moreover, treatment with U0126/Ly294002 downregulated EZH2/EZH1 expression, and upregulated JMJD3/UTX expression. The effects of U0126/Ly294002 were nullified when EZH2/EZH1 was overexpressed or when JMJD3/UTX was inhibited in the SKM-1 cells. Treatment with U0126/Ly294002 also resulted in a decreased H3K27me3 protein level and H3K27me3 level in the DLX5 promoter region, leading to an increased DLX5 expression. Overall, the findings of the present study suggest that U0126/Ly294002 participates in MDS-AML transformation by modulating the levels of H3K27me3 methylases and de-methylases, and regulating DLX5 transcription and expression.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

MEK/ERK and PI3K/AKT pathway inhibitors affect the transformation of myelodysplastic syndrome into acute myeloid leukemia via H3K27me3 methylases and de‑methylases

Zheng,

Chen,

Zhang

et al. 2023

Int J Oncol

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“…SKM-1 cells have not been a widely employed as a AML-MDS biological model in research. Nevertheless, the range of research areas in which they have been exploited includes induction of cell death [62,63], proliferation [64] and cell cycle [65,66], differentiation [67,68], gene expression [69] and its epigenetic regulation [70] or drug resistance [71], usually as a response to a particular substance [72] or nanoconjugates [73,74].…”

Section: Introductionmentioning

confidence: 99%

Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS₂-based nanoconjugates

et al. 2021

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Acute myeloid leukemia (AML) is a highly aggressive type of cancer caused by the uncontrolled proliferation of undifferentiated myeloblasts, affecting the bone marrow and blood. Systemic chemotherapy is considered the primary treatment strategy; unfortunately, healthy cells are also affected to a large extent, leading to severe side effects of this treatment. Targeted drug therapies are becoming increasingly popular in modern medicine, as they bypass normal tissues and cells. Two-dimensional MoS2-based nanomaterials have attracted attention in the biomedical field as promising agents for cancer diagnosis and therapy. Cancer cells typically (over)express distinctive cytoplasmic membrane-anchored or -spanning protein-based structures (e.g., receptors, enzymes) that distinguish them from healthy, non-cancerous cells. Targeting cancer cells via tumor-specific markers using MoS2-based nanocarriers loaded with labels or drugs can significantly improve specificity and reduce side effects of such treatment. SKM-1 is an established AML cell line that has been employed in various bio-research applications. However, to date, it has not been used as the subject of studies on selective cancer targeting by inorganic nanomaterials. Here, we demonstrate an efficient targeting of AML cells using MoS2 nanoflakes prepared by a facile exfoliation route and functionalized with anti-CD33 antibody that binds to CD33 receptors expressed by SKM-1 cells. Microscopic analyses by confocal laser scanning microscopy supplemented by label-free confocal Raman microscopy proved that (anti-CD33)-MoS2 conjugates were present on the cell surface and within SKM-1 cells, presumably having been internalized via CD33-mediated endocytosis. Furthermore, the cellular uptake of SKM-1 specific (anti-CD33)-MoS2 conjugates assessed by flow cytometry analysis was significantly higher compared with the cellular uptake of SKM-1 nonspecific (anti-GPC3)-MoS2 conjugates. Our results indicate the importance of appropriate functionalization of MoS2 nanomaterials by tumor-recognizing elements that significantly increase their specificity and hence suggest the utilization of MoS2-based nanomaterials in the diagnosis and therapy of AML.

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“…In addition, DDX23 was suspected to be involved in myelodysplastic syndrome. The pharmacological restoration of DDX23 might be a potential therapeutic approach for myelodysplastic syndrome [ 24 ]. Therefore, DDX23 is differentially expressed and demonstrates different roles in various human cancers.…”

Section: Discussionmentioning

confidence: 99%

METTL3 enhances pancreatic ductal adenocarcinoma progression and gemcitabine resistance through modifying DDX23 mRNA N6 adenosine methylation

Lin

Wang

et al. 2023

Cell Death Dis

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The aim of the present study was to clarify the mechanism of how METTL3 regulated pancreatic ductal adenocarcinoma (PDAC) progression by m6A modification of its downstream target mRNA and signaling pathway. Immunoblotting and qRT-PCR assays was employed to determine the expression levels of METTL3. In situ fluorescence hybridization was conducted to localize the cellular distribution of METTL3 and DEAD-box helicase 23 (DDX23). CCK8, colony formation, EDU incorporation, TUNEL, wound healing and Transwell assays were carried out accordingly to study the viability, proliferation, apoptosis, and mobility of cells under different treatments in vitro. Xenograft and animal lung metastasis experiments were also conducted to study the functional role of METTL3 or DDX23 on tumor growth and lung metastasis in vivo. MeRIP-qPCR and bioinformatical analyses were used to obtain the potential direct targets of METTL3. It was shown that m6A methyltransferase METTL3 was upregulated in PDAC tissues with gemcitabine resistance, and its knockdown sensitized pancreatic cancer cells to chemotherapy. Furthermore, silencing METTL3 remarkably reduced pancreatic cancer cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, validation experiments confirmed that DDX23 mRNA was a direct target of METTL3 in YTHDF1-dependent manner. Additionally, DDX23 silence resulted in the suppression of pancreatic cancer cell malignancy and PIAK/Akt signaling inactivation. Strikingly, rescuse experiments demonstrated the inhibitive effects of METTL3 silence on cell phenotypes and gemcitabine resistance were partially reversed by forcibly expressed DDX23. In summary, METTL3 promotes PDAC progression and gemcitabine resistance by modifying DDX23 mRNA m6A methylation and enhancing PI3K/Akt signaling activation. Our findings establish a potential tumor promotive and chemo-resistant role for METTL3/DDX23 axis in PDAC.

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4-Amino-2-trifluoromethyl-phenyl retinate induced differentiation of human myelodysplastic syndromes SKM-1 cell lines by up-regulating DDX23

Cited by 5 publications

References 38 publications

MEK/ERK and PI3K/AKT pathway inhibitors affect the transformation of myelodysplastic syndrome into acute myeloid leukemia via H3K27me3 methylases and de‑methylases

MEK/ERK and PI3K/AKT pathway inhibitors affect the transformation of myelodysplastic syndrome into acute myeloid leukemia via H3K27me3 methylases and de‑methylases

Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS₂-based nanoconjugates

METTL3 enhances pancreatic ductal adenocarcinoma progression and gemcitabine resistance through modifying DDX23 mRNA N6 adenosine methylation

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4-Amino-2-trifluoromethyl-phenyl retinate induced differentiation of human myelodysplastic syndromes SKM-1 cell lines by up-regulating DDX23

Cited by 5 publications

References 38 publications

MEK/ERK and PI3K/AKT pathway inhibitors affect the transformation of myelodysplastic syndrome into acute myeloid leukemia via H3K27me3 methylases and de‑methylases

MEK/ERK and PI3K/AKT pathway inhibitors affect the transformation of myelodysplastic syndrome into acute myeloid leukemia via H3K27me3 methylases and de‑methylases

Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS2-based nanoconjugates

METTL3 enhances pancreatic ductal adenocarcinoma progression and gemcitabine resistance through modifying DDX23 mRNA N6 adenosine methylation

Contact Info

Product

Resources

About

Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS₂-based nanoconjugates