Background: Myelodysplastic syndrome (MDS) is a haematopoietic malignancy that is characterized by a heterogeneous clinical course and dysplastic maturation of blood lineages. Immune dysregulation has gained attention as one of the fundamental mechanisms responsible for the development of MDS. This study aimed to screen immunerelated biomarkers and pathways in MDS. Methods: Differentially expressed mRNAs (DE-mRNAs) and differentially expressed microRNAs (DE-miRNAs) in different subtypes of MDS were sourced from the Gene Expression Omnibus (GEO) database. DE-mRNAs were intersected with immune-related gene sets to collect immune-related mRNAs, which were put into the Search Tool for the Retrieval of Interacting Genes (STRING) to construct protein-protein interaction (PPI) networks. Target mRNAs of DE-miRNAs were predicted using the miRDB database and intersected with screened immune-related mRNAs to construct miRNA-mRNA interaction networks. Topological analysis of constructed networks was applied to screen key molecules, which were assessed in independent datasets and previous literature. Enrichment analysis was applied to screen dysregulated pathways in MDS. Results: Screened key mRNAs were mainly from the Toll-like receptor (TLR) family, including TLR2, TLR4, TLR7, and from the chemokine family, including C-X-C motif chemokine ligand 10 (CXCL10) and CC chemokine ligand 4 (CCL4). Cytokine-cytokine receptor interactions were among the major pathways in the enrichment analysis results. Hsa-miR-30b, hsa-miR-30e and hsa-miR-221 were validated as key miRNAs and modulate cytokine-cytokine receptor interactions by targeting immune-related mRNAs. Conclusion: Dysregulated cytokines reflect the immunization status in MDS. Immune-related miRNA-mRNA interactions not only provide a perspective to our understanding of immunologic derangement in the pathogenesis of MDS but also provide new therapeutic opportunities.

Acyl-CoA thioesterase (ACOT) plays a considerable role in lipid metabolism, which is closely related to the occurrence and development of cancer, nevertheless, its role has not been fully elucidated in acute myeloid leukemia (AML). To explore the role of ACOT2 in AML and to provide a potential therapeutic target for AML, the expression pattern of ACOT was investigated based on the TNMplot, Gene Expression Profiling Interactive Analysis (GEPIA), and Cancer Cell Line Encyclopedia (CCLE) database, and diagnostic value, prognostic value, and clinical phenotype of ACOT were explored based on data from The Cancer Genome Atlas (TCGA). Functional annotation and enrichment analysis of the common targets between ACOT2 coexpressed and AML-related genes were further performed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses. The protein-protein interaction (PPI) network of ACOT2 coexpressed genes and functional ACOT2-related metabolites association network were constructed based on GeneMANIA and Human Metabolome Database. Among ACOTs, ACOT2 was highly expressed in AML compared to normal control subjects according to TNMplot, GEPIA, and CCLE database, which was significantly associated with poor overall survival (OS) in AML ( P = 0.003 ). Moreover, ACOT2 exhibited excellent diagnostic efficiency for AML (AUC: 1.000) and related to French-American-British (FAB) classification and cytogenetics. GO, KEGG, and GSEA analyses of 71 common targets between ACOT2 coexpressed and AML-related genes revealed that ACOT2 is closely related to ACOT1, ACOT4, enoyl-acyl carrier protein reductase, mitochondrial (MECR), puromycin-sensitive aminopeptidase (NPEPPS), SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and long-chain fatty acid-CoA ligase 1 (ACSL1) in PPI network, and plays a significant role in lipid metabolism, that is, involved in fatty acid elongation and biosynthesis of unsaturated fatty acids. Collectively, the increase of ACOT2 may be an important characteristic of worse OS and abnormal lipid metabolism, suggesting that ACOT2 may become a potential therapeutic target for AML.

Zinc oxide nanoparticles (ZnO NPs) have exhibited excellent anti‐tumor properties; the present study aimed to elucidate the underlying mechanism of ZnO NPs induced apoptosis in acute myeloid leukemia (AML) cells by regulating mitochondrial division. THP‐1 cells, an AML cell line, were first incubated with different concentrations of ZnO NPs for 24 hr. Next, the expression of Drp‐1, Bcl‐2, Bax mRNA, and protein was detected, and the effects of ZnO NPs on the levels of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), apoptosis, and ATP generation in THP‐1 cells were measured. Moreover, the effect of Drp‐1 inhibitor Mdivi‐1 and ZnO NPs on THP‐1 cells was also detected. The results showed that the THP‐1 cells survival rate decreased with the increment of ZnO NPs concentration and incubation time in a dose‐ and time‐dependent manner. ZnO NPs can reduce the cell Δψm and ATP levels, induce ROS production, and increase the levels of mitochondrial division and apoptosis. In contrast, the apoptotic level was significantly reduced after intervention of Drp‐1 inhibitor, suggesting that ZnO NPs can induce the apoptosis of THP‐1 cells by regulating mitochondrial division. Overall, ZnO NPs may provide a new basis and idea for treating human acute myeloid leukemia in clinical practice.

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