Extracellular matrix protein 1 (ECM1) is related to strong invasiveness and poor prognosis in major malignancies, but the underlying mechanism remains unknown. Here we aimed to elucidate the function of ECM1 on cell metastasis and glucose metabolism in gastric cancer (GC). The level of ECM1 in sera and tissues of patient with GC were positively correlated with tumor invasion and recurrence. Genetic manipulation of ECM1 expression affected cell metastasis and glucose metabolism in GC cell lines. Enhanced ECM1 expression facilitated gene expression levels associated with epithelial-mesenchymal transition (EMT) and glucose metabolism. Interestingly, our results indicated that ECM1 directly interacted with integrin β4 (ITGB4) and activated ITGB4/focal adhesion kinase (FAK)/glycogen synthase kinase 3β signaling pathway, which further induced the expression of transcription factor SOX2. Aberrant expression of SOX2 altered gene expression of EMT factors and glucose metabolism enzymes. Furthermore, SOX2 enhanced hypoxia-inducible factor α (HIF-1α) promoter activity to regulate glucose metabolism. The micro-positron emission tomography/computed tomography imaging of xenograft model showed that ECM1 substantially increased F-fluorodeoxyglucose uptake in xenograft tumors. Using in vivo mouse tail vein injection experiments, ECM1 was also found to increase in lung surface metastasis. These findings provide evidence that ECM1 regulates GC cell metastasis and glucose metabolism by inducing ITGB4/FAK/SOX2/HIF-1α signal pathway and have important implications for the development of therapeutic target to prevent tumor metastasis and recurrence.
BackgroundChromobox protein homolog 7 (CBX7), a member of the polycomb group (PcG) family of proteins, is involved in the regulation of cell proliferation and cancer progression. PcG family members, such as BMI, Mel-18, and EZH2, are integral constituents of the polycomb repressive complexes (PRCs) and have been known to regulate cancer stem cell (CSC) phenotype. However, the role of other PRCs’ constituents such as CBX7 in the regulation of CSC phenotype remains largely elusive. This study was to investigate the role of CBX7 in regulating stem cell-like properties of gastric cancer and the underlying mechanisms.MethodsFirstly, the role of CBX7 in regulating stem cell-like properties of gastric cancer was investigated using sphere formation, Western blot, and xenograft tumor assays. Next, RNA interference and ectopic CBX7 expression were employed to determine the impact of CBX7 on the expression of CSC marker proteins and CSC characteristics. The expression of CBX7, its downstream targets, and stem cell markers were analyzed in gastric stem cell spheres, common cancer cells, and gastric cancer tissues. Finally, the pathways by which CBX7 regulates stem cell-like properties of gastric cancer were explored.ResultsWe found that CBX7, a constituent of the polycomb repressive complex 1 (PRC1), plays an important role in maintaining stem cell-like characteristics of gastric cancer cells via the activation of AKT pathway and the downregulation of p16. Spearman rank correlation analysis showed positive correlations among the expression of CBX7 and phospho-AKT (pAKT), stem cell markers OCT-4, and CD133 in gastric cancer tissues. In addition, CBX7 was found to upregulate microRNA-21 (miR-21) via the activation of AKT-NF-κB pathway, and miR-21 contributes to CBX7-mediated CSC characteristics.ConclusionsCBX7 positively regulates stem cell-like characteristics of gastric cancer cells by inhibiting p16 and activating AKT-NF-κB-miR-21 pathway.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0562-z) contains supplementary material, which is available to authorized users.
We aimed to determine the prevalence of the coexistence of HBsAg and anti-HBs and to analyze the clinical and virological features of infection, including amino acid (aa) patterns of the S gene and reverse transcriptase (RT) region in Chinese chronic hepatitis B (CHB) patients. Fifty-four (2.90%) CHB patients who were positive for both HBsAg and anti-HBs were tested, and sequences were obtained from 52 of them as well as 48 patients from a control group. S gene and RT region sequences were amplified and sequenced using in-house protocols. There was no significant difference between patients with and without anti-HBs with regard to age, gender, alanine aminotransferase level, and the proportion positive for HBeAg and HBcAb. The occurrence of genotype C (P = 0.001) and anti-HBeAb positivity (P = 0.027) was significantly higher in HBsAg+/anti-HBs+ individuals. In the S gene, the number of mutated residues in the HBsAg+/anti-HBs+ group was markedly higher than in control patients (1.88 versus 1.02 substitutions per 100 amino acids, P = 0.022). The amino acid exchange occurred mostly within the N-terminal region (2.15 versus 0.87 substitutions per 100 amino acids, P = 0.023) and the "a" determinant (3.61 versus 1.56 substitutions per 100 amino acids, P = 0.049) in the two groups. In the RT region, the mean number of substitution per 100 aa showed a tendency to be significantly higher in HBsAg+/anti-HBs+ patients than in controls (2.34 versus 1.46, P = 0.040). This study showed a prevalence of coexistence of anti-HBs in HBsAg-positive patients and an increased frequency of genotype C and aa variability within both HBsAg and RT involving functionally important regions of those proteins.
Developing
hydrogel wound dressings with antibacterial activity
and reproducible adhesion ability is an urgent need in biomaterial
sciences. However, present hydrogel wound dressings either employ
inorganic antibacterial agents such as Ag and metallic oxide nanoparticles,
which have dosage dependence and unsatisfactory biocompatibility,
or load antibiotics, evolving drug-resistant bacteria. Here a nucleobase-inspired
self-adhesive and inherently antibacterial hydrogel is reported as
a wound dressing. The hydrogel was developed from poly(3-dimethyl(methacryloyloxyethyl)ammonium
propanesulfonate)-co-poly(methacryloylamidoadenine)
(PDMAPS-co-PMA-Ade) and chitosan. The DMAPS moieties
endow the hydrogel with an anti-fouling property, while special interactions
between nucleobase-modified MA-Ade provide facile molecular recognition
with corresponding groups on the surface of tissues. In vivo cutaneous
wound repair determination demonstrated that the hydrogel-treated
mice showed no hemorrhage, less inflammation, and fewer neovessels
than the control after 14 days. This achievement offers an opportunity
to facilitate significant wound healing without the aid of other antibiotics.
The effect of plant invasion on the microorganisms of soil sediments is very important for estuary ecology. The community structures of methanogens and sulfate-reducing bacteria (SRB) as a function of Spartina alterniflora invasion in Phragmites australis-vegetated sediments of the Dongtan wetland in the Yangtze River estuary, China, were investigated using 454 pyrosequencing and quantitative real-time PCR (qPCR) of the methyl coenzyme M reductase A (mcrA) and dissimilatory sulfite-reductase (dsrB) genes. Sediment samples were collected from two replicate locations, and each location included three sampling stands each covered by monocultures of P. australis, S. alterniflora and both plants (transition stands), respectively. qPCR analysis revealed higher copy numbers of mcrA genes in sediments from S. alterniflora stands than P. australis stands (5- and 7.5-fold more in the spring and summer, respectively), which is consistent with the higher methane flux rates measured in the S. alterniflora stands (up to 8.01 ± 5.61 mg m−2 h−1). Similar trends were observed for SRB, and they were up to two orders of magnitude higher than the methanogens. Diversity indices indicated a lower diversity of methanogens in the S. alterniflora stands than the P. australis stands. In contrast, insignificant variations were observed in the diversity of SRB with the invasion. Although Methanomicrobiales and Methanococcales, the hydrogenotrophic methanogens, dominated in the salt marsh, Methanomicrobiales displayed a slight increase with the invasion and growth of S. alterniflora, whereas the later responded differently. Methanosarcina, the metabolically diverse methanogens, did not vary with the invasion of, but Methanosaeta, the exclusive acetate utilizers, appeared to increase with S. alterniflora invasion. In SRB, sequences closely related to the families Desulfobacteraceae and Desulfobulbaceae dominated in the salt marsh, although they displayed minimal changes with the S. alterniflora invasion. Approximately 11.3 ± 5.1% of the dsrB gene sequences formed a novel cluster that was reduced upon the invasion. The results showed that in the sediments of tidal salt marsh where S. alterniflora displaced P. australis, the abundances of methanogens and SRB increased, but the community composition of methanogens appeared to be influenced more than did the SRB.
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