The prognostic value of matrix metalloproteinase‐7 and matrix metalloproteinase‐15 in acute myeloid leukemia

Wu, Yingjie; S, Pan; Leng, Jun; Xie, Tian; Jamal, Muhammad; Yin, Qian; Li, Jingyuan; He, Chunjiang; Dong, Xin; Shao, Liang; Zhang, Qiuping

doi:10.1002/jcb.28351

Cited by 14 publications

(9 citation statements)

References 53 publications

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“…Interestingly, we have also identified the matrix metalloproteinase Mmp2, an extracellular protease responsible for extracellular matrix (ECM) degradation. Its mammalian counterpart MMP15 (aka MT2-MMP) is apparently expressed in several myeloid cell lines and in AML samples, which suggests a contribution to the invasiveness properties of NA9-mediated leukemia [88,89].…”

Section: A Role In Cell Polarity / Basement Membrane Organizationmentioning

confidence: 99%

A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene

et al. 2021

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Acute myeloid leukemia (AML) underlies the uncontrolled accumulation of immature myeloid blasts. Several cytogenetic abnormalities have been associated with AML. Among these is the NUP98-HOXA9 (NA9) translocation that fuses the Phe-Gly repeats of nucleoporin NUP98 to the homeodomain of the transcription factor HOXA9. The mechanisms enabling NA9-induced leukemia are poorly understood. Here, we conducted a genetic screen in Drosophila for modifiers of NA9. The screen uncovered 29 complementation groups, including genes with mammalian homologs known to impinge on NA9 activity. Markedly, the modifiers encompassed a diversity of functional categories, suggesting that NA9 perturbs multiple intracellular events. Unexpectedly, we discovered that NA9 promotes cell fate transdetermination and that this phenomenon is greatly influenced by NA9 modifiers involved in epigenetic regulation. Together, our work reveals a network of genes functionally connected to NA9 that not only provides insights into its mechanism of action, but also represents potential therapeutic targets.

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Section: A Role In Cell Polarity / Basement Membrane Organizationmentioning

confidence: 99%

A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene

et al. 2021

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“…It was reported that MMP14 is the target of BCR-ABL/ABL interactor 1 (Abi 1) signaling, and induces increased motility and invasiveness leukemic cells [ 78 ]. MMP15 is highly expressed in AML patients and was correlated with poor overall survival [ 79 ]. Downregulation of MMP14 and MMP15 by 8-OHD may indicate that it possesses anti-metastatic activity ( Figure 4 c,d).…”

Section: Resultsmentioning

confidence: 99%

8-Hydroxydaidzein Downregulates JAK/STAT, MMP, Oxidative Phosphorylation, and PI3K/AKT Pathways in K562 Cells

Wang

Chen

et al. 2021

Biomedicines

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A metabolite isolated from fermented soybean, 8-hydroxydaidzein (8-OHD, 7,8,4′-trihydroxyisoflavone, NSC-678112), is widely used in ethnopharmacological research due to its anti-proliferative and anti-inflammatory effects. We reported previously that 8-OHD provoked reactive oxygen species (ROS) overproduction, and induced autophagy, apoptosis, breakpoint cluster region-Abelson murine leukemia viral oncogene (BCR-ABL) degradation, and differentiation in K562 human chronic myeloid leukemia (CML) cells. However, how 8-OHD regulates metabolism, the extracellular matrix during invasion and metastasis, and survival signaling pathways in CML remains largely unexplored. High-throughput technologies have been widely used to discover the therapeutic targets and pathways of drugs. Bioinformatics analysis of 8-OHD-downregulated differentially expressed genes (DEGs) revealed that Janus kinase/signal transducer and activator of transcription (JAK/STAT), matrix metalloproteinases (MMPs), c-Myc, phosphoinositide 3-kinase (PI3K)/AKT, and oxidative phosphorylation (OXPHOS) metabolic pathways were significantly altered by 8-OHD treatment. Western blot analyses validated that 8-OHD significantly downregulated cytosolic JAK2 and the expression and phosphorylation of STAT3 dose- and time-dependently in K562 cells. Zymography and transwell assays also confirmed that K562-secreted MMP9 and invasion activities were dose-dependently inhibited by 8-OHD after 24 h of treatment. RT-qPCR analyses verified that 8-OHD repressed metastasis and OXPHOS-related genes. In combination with DisGeNET, it was found that 8-OHD’s downregulation of PI3K/AKT is crucial for controlling CML development. A STRING protein–protein interaction analysis further revealed that AKT and MYC are hub proteins for cancer progression. Western blotting revealed that AKT phosphorylation and nuclear MYC expression were significantly inhibited by 8-OHD. Collectively, this systematic investigation revealed that 8-OHD exerts anti-CML effects by downregulating JAK/STAT, PI3K/AKT, MMP, and OXPHOS pathways, and MYC expression. These results could shed new light on the development of 8-OHD for CML therapy.

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“…MMP-7 was found to be upregulated in patients with AML, especially in patients who had relapsed (36). Wu et al also suggested that higher levels of expression of MMP7 can predict poor OS in AML (37). PDCD1 (PD-1, Programmed Cell Death 1 Protein) has been found to be highly expressed in many cancers and was found to be responsible for the escaping of cancer cells from immunosurveillance.…”

Section: Discussionmentioning

confidence: 99%

Identification of an Immune-Related Gene Signature Based on Immunogenomic Landscape Analysis to Predict the Prognosis of Adult Acute Myeloid Leukemia Patients

et al. 2020

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Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by highly heterogeneous molecular lesions and cytogenetic abnormalities. Immune disorders in AML and impaired immune cell function have been found to be associated with abnormal karyotypes in AML patients. Immunotherapy has become an alternative therapeutic method that can improve the outcomes of AML patients. For solid tumors, the expression patterns of genes associated with the immune microenvironment provide valuable prognostic information. However, the prognostic roles of immune genes in AML have not been studied as yet. In this study, we identified 136 immune-related genes associated with overall survival in AML patients through a univariate Cox regression analysis using data from TCGA-AML and GTEx datasets. Next, we selected 24 hub genes from among the 136 genes based on the PPI network analysis. The 24 immune-related hub genes further underwent multivariate Cox regression analysis and LASSO regression analysis. Finally, a 6 immune-related gene signature was constructed to predict the prognosis of AML patients. The function of the hub IRGs and the relationships between hub IRGs and transcriptional factors were investigated. We found that higher levels of expression of CSK, MMP7, PSMA7, PDCD1, IKBKG, and ISG15 were associated with an unfavorable prognosis of AML patients. Meanwhile, patients in the TCGA-AML datasets were divided into a high risk score group and a low risk score group, based on the median risk score value. Patients in the high risk group tended to show poorer prognosis [P = 0.00019, HR = 1.89 (1.26–2.83)]. The area under the curve (AUC) was 0.6643. Multivariate Cox Regression assay confirmed that the 6 IRG signature was an independent prognostic factor for AML. The prognostic role of the immune related-gene signature was further validated using an independent AML dataset, GSE37642. In addition, patients in the high risk score group in the TCGA dataset were found to be of an advanced age, IDH mutation, and M5 FAB category. These results suggested that the proposed immune related-gene signature may serve as a potential prognostic tool for AML patients.

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The prognostic value of matrix metalloproteinase‐7 and matrix metalloproteinase‐15 in acute myeloid leukemia

Cited by 14 publications

References 53 publications

A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene

A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene

8-Hydroxydaidzein Downregulates JAK/STAT, MMP, Oxidative Phosphorylation, and PI3K/AKT Pathways in K562 Cells

Identification of an Immune-Related Gene Signature Based on Immunogenomic Landscape Analysis to Predict the Prognosis of Adult Acute Myeloid Leukemia Patients

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