Gastric cancer accounts for a sizeable proportion of global cancer mortality with high morbidity and poor prognosis. Kinesin superfamily proteins (KIFs) are microtubule-dependent motor proteins that function as oncogenes in cancer cells, it has been discovered in recent years. Kinesin family member 2a (KIF2A), a member of the KIFs, has received attention for its role in carcinogenesis and its prognostic value in several human cancers such as breast cancer, colorectal cancer, and squamous cell carcinoma. However, the role of KIF2A in human gastric cancer remains unknown. In this study we aimed to explore the expression and biological functions of KIF2A in human gastric cancer cells, as well as to reveal its potential action mechanism. First, we found that KIF2A was markedly increased in gastric cancer cells (MKN-28, MKN-45, NCI-N87 and SGC-7901) compared to normal gastric mucosa epithelial cells (GES-1). Then KIF2A was successfully silenced in MKN-45 and SGC-7901 cells to facilitate further research into its function. We discovered that KIF2A silencing can significantly inhibit the growth and invasion of MKN-45 and SGC-7901 cells in a time-independent manner, accompanying a decreased expression of Membrane type 1-matrix metalloproteinase (MT1-MMP). When MT1-MMP was reintroduced into MKN-45 and SGC-7901 cells in the KIF2A-siRNA group, only invasion inhibition effects on MKN-45 and SGC-7901 cells induced by KIF2A silencing can be reversed. In conclusion, our study reveals that down-regulation of KIF2A can inhibit gastric cancer cell invasion by suppressing MT1-MMP.
Cardiomyocyte apoptosis is a major cause of myocardial ischemia/reperfusion (MI/R) injury, in which the activation of the signal transducer and activator of transcription 1 (STAT1) plays an important role. The E3-ubiquitin ligase TRIM6 has been implicated in regulating STAT1 activity, however, whether it is associated with MI/R injury and the underlying mechanism are not determined. In this study, by investigating a mouse MI/R injury model, we show that TRIM6 expression is induced in mouse heart following MI/R injury. Additionally, TRIM6 depletion reduces and its overexpression increases myocardial infarct size, serum creatine phosphokinase (CPK) level and cardiomyocyte apoptosis in mice subjected to MI/R injury, indicating that TRIM6 functions to aggravate MI/R injury. Mechanistically, TRIM6 promotes IKKε-dependent STAT1 activation, and the inhibition of IKKε or STAT1 with the specific inhibitor, CAY10576 or fludarabine, abolishes TRIM6 effects on cardiomyocyte apoptosis and MI/R injury. Similarly, TRIM6 mutant lacking the ability to ubiquitinate IKKε and induce IKKε/STAT1 activation also fails to promote cardiomyocyte apoptosis and MI/R injury. Thus, these results suggest that TRIM6 aggravates MI/R injury through promoting IKKε/STAT1 activation-dependent cardiomyocyte apoptosis, and that TRIM6 might represent a novel therapeutic target for alleviating MI/R injury.
Mesenchymal stem cells (MSCs) have the potential for self-renewal and multipotential differentiation to regenerate damaged tissues or recover functional absence in diseases. Superparamagnetic iron oxide nanoparticles (SPIONs) are used as contrast agents in magnetic resonance imaging (MRI) for labeling cells in vitro and for tracking SPION-labeled cells after transplantation in vivo. Human amniotic membrane-derived mesenchymal stem cells (hAM-dMSCs) have the capacity for neuron-like differentiation that could be used to cure central nervous system (CNS) diseases. The study investigated the impacts of cytotoxicity of SPIONs on neuron-like differentiation of hAM-dMSCs in both single (1×) and multiple (4×) SPIONs-labeled methods. hAM-dMSCs could be efficiently labeled at safe concentrations of SPIONs (≤14 μg/ml) without significantly affecting their viability (>80% after a MTT assay), special surface antigens (CD29, CD44, CD90, CD105 through flow cytometry), and neuron-like differentiation (nestin and neuron-specific enolase through immunocytochemistry and reverse transcription polymerase chain reaction). Compared with multiple (4×) SPION-labeled methods, a single (1×) SPION-labeled method avoided multiple SPION-labeled hAM-dMSCs and minimized the impact of cytotoxicity of SPIONs on neuron-like differentiation of hAM-dMSCs. Under safe concentrations of SPIONs, a single (1×) SPION-labeled method provided appropriate viability for SPIONs-labeled hAM-dMSCs and facilitated the MRI evaluation of hAM-dMSCs after transplantation.
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