Basing on microRNA-mRNA analysis identifies microRNA in exosomes associated with wound repair of diabetic ulcers

The diabetic ulcer is one of the serious complications of diabetes.In this study,we aimed to establish an exosomal microRNA(miRNA)-targetedmessenger RNA(mRNA)regulatory network for screening new biomarkers for diabetic ulcer treatment.For this purpose,exosomes were extracted from bone marrow stem cells(BMSCs)collected from diabetic ulcer patients and healthy adults.The miRNAs in exosomes was detected by high-throughput sequencing analysis.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the differential miRNAs were performed.The miRNA-mRNA regulatory network between candidate miRNAs and their target genes were constructed by Cytoscape software basing on mRNA expression profiles data of diabetic ulcer patients from Gene Expression Omnibus(GEO).GO and KEGG analyses of the core genes were performed.A total of 63 differential expressed miRNAs in BMSCs exosomes were identified between diabetic ulcer patients and healthy adults.The GO analysis of miRNAs showed that it was mainly related to signal transduction and intercellular transport,and KEGG analysis showed that it was related to the vascular endothelial growth factor(VEGF)signaling pathway.The core genes of the miRNA-mRNA network were thioredoxin interacting protein(TXNIP),cell division cycle 14A(CDC14A),cache domain containing 1(CACHD1),interferon-induced protein 44 like(IFI44L),late cornified envelope 1AL(CE1A),leucine-rich repeats and immunoglobulin-like domains 2(LRIG2),palmdelphin(PALMD)and serine and arginine-rich splicing factor 11(SRSF11).GO analysis of the core genes was related to platelet-derived growth factor receptor signaling pathway.The KEGG analysis of the core genes was related to the cell cycle and nucleotide-binding oligomerization domain(NOD)-like receptor signaling pathway.A potential miRNA-mRNA regulatory network provides a comprehensive understanding of the molecular mechanisms and promising new targets such as miR-130a-5p,SESN2,LRIG2,and CDC14A for the wound repair of diabetic ulcers.

Transient axonal glycoprotein-1 induces apoptosisrelated gene expression without triggering apoptosis in U251 glioma cells

Previous studies show that transient axonal glycoprotein-1, a ligand of amyloid precursor pro- tein, increases the secretion of amyloid precursor protein intracellular domain and is involved in apoptosis in Alzheimer＇s disease. In this study, we examined the effects of transient axonal glyco- protein-1 on U251 glioma cells. 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay showed that transient axonal glycoprotein-1 did not inhibit the proliferation of U251 cells, but promoted cell viability. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that transient axonal glycoprotein-1 did not induce U251 cell apoptosis. Real-time PCR revealed that transient axonal glycoprotein-1 substantially upregulated levels of amyloid precursor protein intracellular C-terminal domain, and p53 and epidermal growth factor recep- tor mRNA expression. Thus, transient axonal glycoprotein-1 increased apoptosis-related gene expression in U251 cells without inducing apoptosis. Instead, transient axonal glycoprotein-1 promoted the proliferation of these glioma cells.

The antiferroptotic role of TRIM7:Molecular mechanism and synergistic effect with temozolomide

Ferroptosis is a distinct form of regulated cell death characterized by the accumulation of lipid peroxides and iron-dependent membrane damage that is a significant contributor to drug resistance in glioblastoma(GBM).Dysregulated iron metabolism is a hallmark of cancer,making ferroptosis a unique potential target for anticancer therapy.Ferritinophagy,the selective autophagy of ferritin,plays an essential role in cellular iron homeostasis and may impact the vulnerability of cells to ferroptosis.Nuclear receptor coactivator 4(NCOA4)protein is a selective cargo receptor that plays a crucial role in ferritinophagy by targeting and delivering the ferritin iron storage protein to the lysosome for degradation,releasing iron[1].However,the underlying molecular mechanism that causes reduced NCOA4 expression in glioma is not fully understood.