RESUMO
AIMS: Sex-determining region of Y chromosome-related high-mobility-group box 15 (SOX15) has recently emerged as a candidate tumor-inhibitor in multiple types of human tumors. To date, the involvement of SOX15 in glioma is undetermined. The purpose of this study was to investigate the expression, function and potential molecular mechanism of SOX15 in glioma. MAIN METHODS: Relative mRNA expression was analyzed by real-time quantitative PCR. Protein expression was determined by Western blot. Cell proliferation was assessed by cell counting kit-8 and colony formation assay. Cell invasion was evaluated by Matrigel invasion assay. Wnt/ß-catenin activation was monitored by luciferase reporter assay. KEY FINDINGS: SOX15 expression was decreased in glioma tissues and cell lines compared with normal controls. Kaplan-Meier analysis revealed that patients with low expression of SOX15 had shorter survival than those who had high expression of SOX15. The upregulation of SOX15 markedly repressed the proliferation and invasion of glioma cells, whereas its depletion enhanced glioma cell proliferation and invasion. Research into the mechanism revealed that SOX15 exerted an inhibitory effect on Wnt/ß-catenin signaling in glioma cells. Notably, overexpression of ß-catenin partially reversed the SOX15 overexpression-mediated tumor-suppressive effect. In addition, SOX15 overexpression significantly impeded tumor formation by glioma cells in vivo in a mouse xenograft model associated with downregulation of active ß-catenin expression. SIGNIFICANCE: These data demonstrate that SOX15 functions as a potential tumor-suppressor in glioma by inhibiting cell proliferation and invasion via the downregulation of Wnt/ß-catenin signaling.
Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Fatores de Transcrição SOX/genética , Via de Sinalização Wnt/genética , Animais , Neoplasias Encefálicas/genética , Proliferação de Células/genética , Regulação para Baixo , Glioma/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Taxa de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismoRESUMO
MicroRNA940 (miR940) has been extensively studied in the pathogenesis of numerous types of human cancer; however, the expression pattern, roles and molecular mechanisms underlying the regulatory actions of miR940 in glioma remain unknown. The present study aimed to further investigate miR940 by studying its expression, roles and mechanisms of action in glioma. Reverse transcriptionquantitative polymerase chain reaction (RTqPCR) was used to detect miR940 expression in glioma tissues and cell lines. The regulatory effects of miR940 in glioma cell proliferation and invasion were determined using MTT and cell invasion assays. Bioinformatics analyses was performed to identify the potential target of miR940, which was further confirmed by luciferase reporter assay, RTqPCR and western blot analysis. In the present study, significantly increased miR940 expression levels were observed in glioma tissues and cell lines compared with normal brain tissues and normal human astrocytes, respectively. Decreased miR940 expression levels attenuated glioma cell proliferation and invasion in vitro. Kruppellike factor 9 (KLF9) was predicted as a potential target of miR940. Further assays demonstrated that miR940 negatively regulated KLF9 expression in glioma cells by directly targeting the 3'untranslated regions of KLF9. Additionally, KLF9 expression was downregulated in glioma tissues and was inversely correlated with miR940. Furthermore, KLF9 knockdown was able to rescue the effects of miR940 on glioma cell proliferation and invasion. The results of the present study suggest that miR940 may function as an oncogene in glioma by targeting KLF9 and may be a considered a therapeutic target for the treatment of gliomas.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/genética , Idoso , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Movimento Celular , Feminino , Seguimentos , Glioma/genética , Glioma/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Células Tumorais CultivadasRESUMO
Green nanocomposites containing biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and cellulose nanocrystals/silver (CNC-Ag) nanohybrids were synthesized and their properties were investigated. It was found that homogeneously dispersed CNC-Ag could act as bifunctional reinforcements to improve the thermal, mechanical and antibacterial properties of PHBV. Compared to pristine PHBV, the tensile strength and the maximum decomposition temperature (Tmax) of the nanocomposite with 10 wt% CNC-Ag were enhanced by 140% and 24.2 °C, respectively. The nanocomposites displayed reduced water uptake and water vapor permeability along with lower migration level in both non-polar and polar simulants compared to the neat biopolymer, which can be related to the increased crystallinity and improved interfacial adhesion. Moreover, the nanocomposites showed strong antibacterial activity against both Gram-negative E. coli and Gram-positive S. aureus. The results of the study indicate that the high performance nanocomposites show great potential applications in the fields of food, beverage packaging and disposable overwrap films.