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BACKGROUND: Microtubule affinity regulating kinase 4 (MARK4), which is overexpressed in various tumors, is involved in the regulation of cell division, proliferation, migration, and the cell cycle, and has been considered a potential marker for cancer; however, its mechanism of action in gastric cancer (GC) remains unclear. This study aimed to investigate the role of MARK4 in the proliferation, migration, and invasion of GC cell through the MAPK/ERK signaling pathway by targeting MARK4 knockdown. METHODS: Using The Cancer Genome Atlas data and clinical information, MARK4 expression and its relationship with prognosis were analyzed. Possible pathways involving MARK4 were explored using enrichment analysis. Western blotting and real-time quantitative polymerase chain reaction were used to detect MARK4 expression in GC. After targeted transfection of siRNA, the transfection efficiency of the experimental group was detected in AGS and HGC-27 cells. The effects of knockdown MARK4 on the proliferation, migration, and invasion of GC cells were verified using CCK-8, colony formation, wound healing, and transwell assays. Finally, the relationship between MARK4, the MAPK/ERK pathway, and epithelial-mesenchymal transition in GC was verified by western blotting. RESULTS: MARK4 expression was upregulated in GC and associated with poor prognosis in patients with GC. Enrichment analysis showed that MARK4 was involved in the activation of the MAPK signaling pathway. Western blotting results indicated that MARK4 overexpression promoted the proliferation, migration, and invasion of GC cells through the MAPK/ERK pathway. CONCLUSION: MARK4 expression was upregulated in GC and promoted the proliferation, migration, and invasion of GC cells through the MAPK/ERK pathway.
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Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Sistema de Señalización de MAP Quinasas , Proteínas Serina-Treonina Quinasas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Sistema de Señalización de MAP Quinasas/genética , Proliferación Celular/genética , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/genética , Fenotipo , Pronóstico , Invasividad Neoplásica/genética , Masculino , Femenino , Persona de Mediana EdadRESUMEN
Cancer development is driven by an accumulation of a small number of driver genetic mutations that confer the selective growth advantage to the cell, while most passenger mutations do not contribute to tumor progression. The identification of these driver genes responsible for tumorigenesis is a crucial step in designing effective cancer treatments. Although many computational methods have been developed with this purpose, the majority of existing methods solely provided a single driver gene list for the entire cohort of patients, ignoring the high heterogeneity of driver events across patients. It remains challenging to identify the personalized driver genes. Here, we propose a novel method (PDRWH), which aims to prioritize the mutated genes of a single patient based on their impact on the abnormal expression of downstream genes across a group of patients who share the co-mutation genes and similar gene expression profiles. The wide experimental results on 16 cancer datasets from TCGA showed that PDRWH excels in identifying known general driver genes and tumor-specific drivers. In the comparative testing across five cancer types, PDRWH outperformed existing individual-level methods as well as cohort-level methods. Our results also demonstrated that PDRWH could identify both common and rare drivers. The personalized driver profiles could improve tumor stratification, providing new insights into understanding tumor heterogeneity and taking a further step toward personalized treatment. We also validated one of our predicted novel personalized driver genes on tumor cell proliferation by vitro cell-based assays, the promoting effect of the high expression of Low-density lipoprotein receptor-related protein 1 (LRP1) on tumor cell proliferation.
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Biología Computacional , Mutación , Neoplasias , Medicina de Precisión , Humanos , Neoplasias/genética , Biología Computacional/métodos , Medicina de Precisión/métodos , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Modelos Genéticos , Bases de Datos GenéticasRESUMEN
In this paper, a novel method was proposed for the synthesis of Cu2S on copper mesh via electrolysis in SRB culture medium. It was found that following electrolysis in SRB medium, squamous-like Cu2S arrays were obtained on the copper mesh, and the Cu2S loading contents varied with the electrolyzing parameters. The resultant Cu2S on copper mesh in SRB (CSCM-SRB) with the highest catalytic MB degradation properties was produced by electrolysis at 3.75 mA/cm2 for 900 s. The optimized MB-degrading conditions were determined to be 1.2 cm2/mL CSCM-SRB with 0.05 M H2O2 at 35 °C when pH = 6, under which the degradation of MB reached over 99% after 120 min of reaction. Disinfecting properties was also proven by antibacterial tests, revealing that an almost 100% antibacterial rate against E. coli was obtained after 8 min. The organic compounds produced by SRB adsorbed on CSCM-SRB strongly promoted the degradation of MB. Furthermore, possible Fenton-like mechanisms of CSCM-SRB were proposed, illustrating that ·O2-, ·OH, and 1O2 acted as the main functional species during Fenton-like reactions, leading to effective MB degradation and high antibacterial properties. Finally, a simple device for wastewater treatment was designed, providing possible applications in real environments.
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MOTIVATION: Cancer is caused by the accumulation of somatic mutations in multiple pathways, in which driver mutations are typically of the properties of high coverage and high exclusivity in patients. Identifying cancer driver genes has a pivotal role in understanding the mechanisms of oncogenesis and treatment. RESULTS: Here, we introduced MaxCLK, an algorithm for identifying cancer driver genes, which was developed by an integrated analysis of somatic mutation data and protein-protein interaction (PPI) networks and further improved by an information entropy index. Tested on pancancer and single cancers, MaxCLK outperformed other existing methods with higher accuracy. About pancancer, we predicted 154 driver genes and 787 driver modules. The analysis of co-occurrence and exclusivity between modules and pathways reveals the correlation of their combinations. Overall, our study has deepened the understanding of driver mechanism in PPI topology and found novel driver genes. AVAILABILITY AND IMPLEMENTATION: The source codes for MaxCLK are freely available at https://github.com/ShandongUniversityMasterMa/MaxCLK-main.
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Biología Computacional , Neoplasias , Humanos , Entropía , Biología Computacional/métodos , Mutación , Redes Reguladoras de Genes , Neoplasias/genética , AlgoritmosRESUMEN
As an influential antifouling material, photocatalytic materials have drawn attention increasingly over recent years owing to their potential bacteriostatic property in the domain of marine antifouling. Herein, a flower-like BiOI@CeO2@Ti3C2 S-scheme photocatalyst was contrived and prepared by hydrothermal method. The innovative combination of Ti3C2 and narrow band gap semiconductor BiOI was implemented to modify CeO2 and the photocatalytic bacteriostatic mechanism of BiOI@CeO2@Ti3C2 was elucidated. Schottky junction was formed between CeO2 and Ti3C2, and a p-n junction was formed between CeO2 and BiOI. By photoelectrochemical characterization, BCT-10 exhibits the best photoelectrochemical performance of which photogenerated carrier transport can be performed more readily at 10 % CeO2@Ti3C2 addition. 99.76 % and 99.89 % of photocatalytic bacteriostatic efficiency of BCT-10 against Escherichia coli and Staphylococcus aureus were implemented respectively, which were 2.98 and 3.07 times higher than that of pure CeO2. The ternary heterojunction can suppress photogenerated electron-hole complexes more effectively and enhance the photocatalytic bacteriostatic effect of CeO2, which also provided a new concept to the further broadened application of CeO2 in the marine bacteriostatic and antifouling field.
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Electrones , Titanio , Escherichia coli , Titanio/farmacologíaRESUMEN
To improve the photocathodic protection performance of traditional TiO2photoanodes for metals, constructing a Z-scheme heterojunction is one of the most promising and creative strategies. Herein, we fabricated a novel Z-scheme MgIn2S4nanosheets/TiO2nanotube nanocomposite through anodization and hydrothermal method. The optimized Z-scheme MgIn2S4/TiO2nanocomposites exhibited stronger visible light absorption, higher separation efficiency of photoelectrons and photocathodic protection performances in comparison to pure TiO2. The theoretical analysis and experimental results show that the Z-scheme heterojunction and oxygen vacancies jointly improved the separation efficiency of photogenerated electron-hole pairs and visible light absorption capacity, thereby improving the photoelectric conversion performance of the MgIn2S4/TiO2nanocomposites. Furthermore, the influence of the precursor solution concentration on the photocathodic protection performances of the composites was investigated. As a result, when the concentration of magnesium source in the precursor solution was 0.06 mmol, the prepared MgIn2S4/TiO2-0.06 displayed the best photocathodic protection performance. In addition, the hydroxyl radicals (·OH) generated in the electron spin resonance (ESR) experiment verified the Z-scheme heterojunction mechanism of the MgIn2S4/TiO2composite, and also demonstrated the excellent redox performance of the composite. This work provides valuable reference for the construction of high-performance Z-scheme heterojunctions for photocathode protection of metals.