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BACKGROUND: RNA methylation modifications, such as N1-methyladenosine/N6-methyladenosine /N5-methylcytosine (m1A/m6A/m5C), are the most common RNA modifications and are crucial for a number of biological processes. Nonetheless, the role of RNA methylation modifications of m1A/m6A/m5C in the pathogenesis of renal interstitial fibrosis (RIF) remains incompletely understood. METHODS: Firstly, we downloaded 2 expression datasets from the GEO database, namely GSE22459 and GSE76882. In a differential analysis of these datasets between patients with and without RIF, we selected 33 methylation-related genes (MRGs). We then applied a PPI network, LASSO analysis, SVM-RFE algorithm, and RF algorithm to identify key MRGs. RESULTS: We eventually obtained five candidate MRGs (WTAP, ALKBH5, YTHDF2, RBMX, and ELAVL1) to forecast the risk of RIF. We created a nomogram model derived from five key MRGs, which revealed that the nomogram model may be advantageous to patients. Based on the selected five significant MRGs, patients with RIF were classified into two MRG patterns using consensus clustering, and the correlation between the five MRGs, the two MRG patterns, and the genetic pattern with immune cell infiltration was shown. Moreover, we conducted GO and KEGG analyses on 768 DEGs between MRG clusters A and B to look into their different involvement in RIF. To measure the MRG patterns, a PCA algorithm was developed to determine MRG scores for each sample. The MRG scores of the patients in cluster B were higher than those in cluster A. CONCLUSIONS: Ultimately, we concluded that cluster A in the two MRG patterns identified on these five key m1A/m6A/m5C regulators may be associated with RIF.
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Algoritmos , Fatores de Transcrição , Humanos , Metilação , Fibrose , RNARESUMO
BACKGROUND AND AIMS: Invasive plants often colonize wide-ranging geographical areas with various local microenvironments. The specific roles of epigenetic and genetic variation during such expansion are still unclear. Chenopodium ambrosioides is a well-known invasive alien species in China that can thrive in metalliferous habitats. This study aims to comprehensively understand the effects of genetic and epigenetic variation on the successful invasion of C. ambrosioides. METHODS: We sampled 367 individuals from 21 heavy metal-contaminated and uncontaminated sites with a wide geographical distribution in regions of China. We obtained environmental factors of these sampling sites, including 13 meteorological factors and the contents of four heavy metals in soils. Microsatellite markers were used to investigate the demographic history of C. ambrosioides populations in China. We also analysed the effect of epigenetic variation on metalliferous microhabitat adaptation using methylation-sensitive amplified polymorphism (MSAP) markers. A common garden experiment was conducted to compare heritable phenotypic variations among populations. KEY RESULTS: Two distinct genetic clusters that diverged thousands of years ago were identified, suggesting that the eastern and south-western C. ambrosioides populations in China may have originated from independent introduction events without recombination. Genetic variation was shown to be a dominant determinant of phenotypic differentiation relative to epigenetic variation, and further affected the geographical distribution pattern of invasive C. ambrosioides. The global DNA unmethylation level was reduced in metalliferous habitats. Dozens of methylated loci were significantly associated with the heavy metal accumulation trait of C. ambrosioides and may contribute to coping with metalliferous microenvironments. CONCLUSIONS: Our study of C. ambrosioides highlighted the dominant roles of genetic variation in large geographical range expansion and epigenetic variation in local metalliferous habitat adaptation.
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Chenopodium ambrosioides , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Ecossistema , Espécies Introduzidas , Epigênese Genética , Variação GenéticaRESUMO
OBJECTIVE AND BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast type of cancer with poor prognosis and high mortality rates. CircRNAs have been widely investigated, due to their crucial role in cancer progression. We aimed to elucidate the function of circPTK2 (has_circ_0003221) in TNBC and explore the mechanism in progression of TNBC. METHODS: qPCR was performed to validate the expression of circPTK2 and related mRNA in TNBC tissue and cell lines. CCK-8, EdU, Transwell assay were conducted to detect the proliferation, migration and invasion of circPTK2 and miR-136 on TNBC cells. RIP and dual-luciferase reporter assay were used to confirm the interaction among circPTK2, miR-136 and NFIB. Si-circPTK2, mimic and inhibitor of miR-136 were transfected in TNBC cells to confirm the mechanism of circPTK2 and miR-136 in TNBC cells. RESULTS: CircPTK2 were downregulated in TNBC tissues and cell lines. CircPTK2 significantly promoted the proliferation, migration, and invasion of TNBC cells. CircPTK2 was confirmed to be a sponge of miR-136, and directly regulated NFBI and AKT/PI3K pathway. A rescue assay validated circPTK2/miR-136/NFIB axis in TNBC cells. CONCLUSION: CircPTK2 promoted TNBC progression and development. circPTK2/miR-136/NFIB might be an effective biomarker for TNBC.
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MicroRNAs , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , RNA Circular/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
BACKGROUND: The role of estrogen receptor ß (ERß) in the pathogenesis and development of breast cancer (BC) is controversial, and it is currently considered to play contradictory roles in different phenotypes. ERß2 is thought to promote the BC process, but its role in triple-negative breast cancer (TNBC) has not been reported. METHODS: In this study, we collected tumor tissues from 15 patients with TNBC and obtained a variety of TNBC cell lines as research objects. The plasmid vectors and RNA interference techniques were used to change the level of target genes in cells, quantitative PCR and Western Blots were used to detect gene expression levels, CCK-8 and EdU assay were used to detect cell growth, and Transwell was used to detect cell migration and invasion. Dual-luciferase gene reports and RNA immunoprecipitation (RIP) were used to verify gene targeting relationships. RESULTS: ERß2 was up-regulated in TNBC tissues and promoted the growth, migration, and invasion of TNBC cells. ERß2 regulated hsa_circ_0000732 expression by binding to SCARF1 promoter. Knockdown of hsa_circ_0000732 inhibited TNBC cell proliferation, migration, and invasion by upregulating miR-1184. CONCLUSION: Our present study found that ERß2 is upregulated in some TNBC cells and promotes TNBC cell growth, migration and invasion by regulating hsa_circ_0000732 targeting miR-1184. The special role of ERß2 in TNBC may be the breakthrough of a targeted treatment strategy for TNBC.
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Receptor beta de Estrogênio/fisiologia , MicroRNAs/fisiologia , RNA Circular/fisiologia , Neoplasias de Mama Triplo Negativas/etiologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Invasividade Neoplásica , Regiões Promotoras Genéticas , Receptores Depuradores Classe F/genética , Neoplasias de Mama Triplo Negativas/patologia , Regulação para CimaRESUMO
A photothermal nanoconfinement reactor (PNCR) system is proposed and demonstrated by using hollow carbon nanospheres (HCNs) to enhance the performance of the chemical reaction. Under light irradiation, the local temperature of the HCN inner void space was much higher than the bulk solution temperature because the confined space concentrates heat and inhibits heat loss. Using the temperature-sensitive model reaction, peroxydisulfate (PDS) activation to oxidize micropollutant, it is shown that the degradation rate of sulfamethoxazole in the PNCR system is 7.1â times of that without nanoconfinement. It is further discovered that the high-quality local heat inside the nanoconfined space shifted the model reaction from an otherwise non-radical pathway to a radical-based pathway. This work provides an interesting strategy to produce a locally high temperature, which has a wide range of applications to energy and environmental fields.
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BACKGROUND: Bladder cancer (BLCA) is a malignant urothelial carcinoma and has a high mortality rate. EPDR1 (ependymin related 1) is a type II transmembrane protein and related to calcium-dependent cell adhesion. METHODS: We explored the potential oncogenic roles of EPDR1 in BLCA basing on the multiple public datasets. RESULTS: We found that EPDR1 expression had a significant difference in BLCA and adjacent normal bladder tissues, and the level of EPDR1was up-regulated with advanced tumor stage and metastasis in BLCA. Meanwhile, the high expression group of EPDR1 had a shorter OS compared to the low or medium expression-group. Furthermore, EPDR1 expression was associated with tumor-infiltrating immune cells (TIICs), including NK cells, CD8 + T cells, CD4 + T cells, Macrophages cells, and so on. Moreover, EPDR1 also involved in several signaling pathways as well as PI3K/AKT pathway, Cytokine receptor interaction, and apoptosis. CONCLUSION: EPDR1 can be used as a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.
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Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Proteínas do Tecido Nervoso/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Correlação de Dados , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , PrognósticoRESUMO
An increasing amount of attention has been given to antimicrobial resistance in the environment because of its substantial threat to human health. The effluent from municipal wastewater treatment plants has been regarded as one of the important sources for the spread of antibiotic resistance genes (ARGs). However, conventional disinfection techniques fail to effectively remove ARGs from effluents. In this work, in situ synthesized hydrated manganese oxide (HMO) coupled with permanganate was applied for the first time in ARG removal from the effluent of wastewater treatment plants. The results show that five ARGs (sulI, sulII, tetQ, tetO, and tetW) as well as the intI1 and 16S rRNA genes had removal efficiencies of 2.46-4.23 logs, which were significantly higher than those obtained by using these reagents individually. This implied that there was a synergistic effect between permanganate and HMO toward the removal of ARGs. Moreover, the contributions of HMO coagulation and permanganate oxidation to ARG removal were semiquantitatively studied, which demonstrated that destruction of the microbial cells by oxidation and removal of the extracellular ARGs released by coagulation were the two main processes in this system. The results of this study provide an alternative method for ARG removal from the effluent of wastewater treatment plants with high efficiencies to control the spreading of ARGs.
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Antibacterianos , Águas Residuárias , Resistência Microbiana a Medicamentos , Genes Bacterianos , Humanos , Compostos de Manganês , Óxidos , RNA Ribossômico 16SRESUMO
Recent developed interfacial solar brine crystallizers, which employ solar-driven water evaporation for salts crystallization from the near-saturation brine to achieve zero liquid discharge (ZLD) brine treatment, are promising due to their excellent energy efficiency and sustainability. However, most existing interfacial solar crystallizers are only tested using NaCl solution and failed to maintain high evaporation capability when treating real seawater due to the scaling problem caused by the crystallization of high-valent cations. Herein, an artificial tree solar crystallizer (ATSC) with a multi-branched and interconnected open-cell cellular structure that significantly increased evaporation surface is rationally designed, achieving an ultra-high evaporation rate (2.30 kg m-2 h-1 during 2 h exposure) and high energy efficiency (128%) in concentrated real seawater. The unit cell design of ATSC promoted salt crystallization on the outer frame rather than the inner voids, ensuring that salt crystallization does not affect the continuous transport of brine through the pores inside the unit cell, thus ATSC can maintain a stable evaporation rate of 1.94 kg m-2 h-1 on average in concentrated seawater for 80 h continuous exposure. The design concept of ATSC represents a major step forward toward ZLD treatment of high-salinity brine in many industrial processes is believed.
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Solid materials with ultra-low thermal conductivity (κ) are of great interest in thermoelectrics for energy conversion or as thermal barrier coatings for thermal insulation. Many low-κ materials exhibit unique properties, such as weak or even insignificant dependence on temperature (T) for κ, i.e., an anomalous glass-like behavior. However, a comprehensive theoretical model elucidating the microscopic phonon mechanism responsible for the glass-like κ-T relationship is still absent. Herein, we take rare-earth tantalates (RE3TaO7) as examples to reexamine phonon thermal transport in defective crystals. By combining experimental studies and atomistic simulations up to 1800 K, we revealed that diffusion-like phonons related to inhomogeneous interatomic bonding contribute more than 70% to the total κ, overturning the conventional understanding that low-frequency phonons dominate heat transport. Furthermore, due to the bridging effects of interatomic bonding, the κ of high-entropy tantalates is not necessarily lower than that of medium-entropy materials, suggesting that attempts to reduce κ through high-entropy engineering are limited, at least in defective fluorite tantalates. The new physical mechanism of multimodal phonon thermal transport in defective structures demonstrated in this work provides a reference for the analysis of phonon transport and offers a new strategy to develop and design low-κ materials by regulating the inhomogeneity of interatomic bonding.
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The prevalence of antibiotic resistance genes (ARGs) in municipal wastewater treatment plants (MWTPs) has emerged as a significant environmental concern. Despite advanced treatment processes, high levels of ARGs persist in the secondary effluent from MWTPs, posing ongoing environmental risks. This study explores the potential of gamma-ray irradiation as a novel approach for sterilizing antibiotic-resistant bacteria (ARB) and reducing ARGs in MWTP secondary effluent. Our findings reveal that gamma-ray irradiation at an absorbed dose of 1.6 kGy effectively deactivates all culturable bacteria, with no subsequent revival observed after exposure to 6.4 kGy and a 96-h incubation in darkness at room temperature. The removal efficiencies for a range of ARGs, including tetO, tetA, blaTEM-1, sulI, sulII, and tetW, were up to 90.5% with a 25.6 kGy absorbed dose. No resurgence of ARGs was detected after irradiation. Additionally, this study demonstrates a considerable reduction in the abundances of extracellular ARGs, with the transformation efficiencies of extracellular tetracycline and sulfadiazine resistance genes decreasing by 56.3-81.8% after 25.6 kGy irradiation. These results highlight the effectiveness of gamma-ray irradiation as an advanced and promising method for ARB sterilization and ARG reduction in the secondary effluent of MWTPs, offering a potential pathway to mitigate environmental risks associated with antibiotic resistance.
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Genes Bacterianos , Águas Residuárias , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genéticaRESUMO
Water resources in the Mekong subregion in Cambodia (MSC) have experienced dramatic changes in past decades, threatening regional ecosystem quality and sustainable development. Thus, it is important to explore the spatiotemporal impacts of climate change and human activities on water resources and ecological sensitivity. This study proposed an effective framework including spatiotemporal analysis of land use/cover change (LUCC) and ecological sensitivity assessment by combining remote sensing (RS) and geographic information system/science (GIS). An optimized feature space and a machine learning classification algorithm were constructed to extract four typical land cover types in the MSC from 1990 to 2020. An ecological sensitivity evaluation system, including four sub-sensitivities calculated by twelve indicators, was then constructed. The results suggest that severe shrinkage of water resources occurred before 2006, decreasing by 21.68%. The correlation between water resources and climate conditions displays a high to low level as human activity becomes involved. A significant spatiotemporal evolutionary pattern of ecological sensitivity was observed under the impact of external interference. Generally, the largest proportion of MSC belongs to the lightly sensitive level, which is mainly concentrated in the lower reaches, with an average of 33.93%. The highly sensitive area with a significant value in ecological protection has a slightly downward trend from 23.72 in 1990 to 22.55% in 2020.
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Mudança Climática , Conservação dos Recursos Naturais , Ecossistema , Recursos Hídricos , Humanos , Camboja , China , Conservação dos Recursos Naturais/métodos , Análise Espaço-TemporalRESUMO
Circular RNAs (circRNAs) contribute to the malignant phenotype and progression of several types of human cancers, including renal cell carcinoma (RCC). This study probed the molecular mechanism of circPGPEP1 regulating RCC proliferation, Warburg effect, and distant metastasis by targeting the miR-378a-3p/JPT1 axis. Here identified higher circPGPEP1 expression in RCC tissues and cells by RT-qPCR, and high levels of circPGPEP1 were positively correlated with high histological grade and distant metastasis in RCC patients. Furthermore, patients with high levels of circPGPEP1 had a worse survival prognosis. Functional assays presented that knockdown of circPGPEP1 inhibited RCC proliferation, invasion, migration, EMT, and Warburg effect. Dual-luciferase reporter assay, RNA immunoprecipitation, nucleoplasmic RNA isolation, and functional rescue experiments confirmed that circPGPEP1 induced JPT1 expression by sponging miR-378a-3p, thereby promoting RCC malignant phenotype. Xenograft assays and metastasis models further demonstrated that down-regulation of circPGPEP1 effectively inhibited tumor growth and distant metastasis of RCC. Taken together, circPGPEP1, a prognostic circRNA in RCC, acts through the miR-378a-3p/JPT1 axis to regulate RCC progression.
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Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Humanos , Carcinoma de Células Renais/genética , Proliferação de Células/genética , Regulação para Baixo , Neoplasias Renais/genética , MicroRNAs/genética , RNA Circular/genética , Piroglutamil-Peptidase I/metabolismoRESUMO
Chenopodium ambrosioides is a manganese (Mn) hyperaccumulator that can be used for Mn-polluted soil phytoremediation. However, the mechanism of Mn tolerance of C. ambrosioides remains largely unknown. In this study, the key factors for Mn tolerance of C. ambrosioides was investigated from the aspects of DNA methylation pattern, gene expression regulation and physiological function. We found that the two genotypes of C. ambrosioides populations have differentiated tolerance to Mn stress (Mn-tolerant: CS and XC, Mn-sensitive: WH). Although there was no difference in Mn accumulation between two types under excess Mn, the biomass and photosynthetic systems were more severely inhibited in Mn-sensitive type, as well as suffering more serious oxidative damage. More differentially expressed genes (DEGs) were downregulated in the Mn-tolerant type, indicating that the Mn-tolerant type tends to inhibit gene expression to cope with Mn stress. DEGs related to metal transport, antioxidant system, phytohormone and transcription factors contribute to the tolerance of C. ambrosioides to Mn, and account for difference in Mn stress sensitivities between the Mn-sensitive and tolerant types. We also found that DNA methylation variation may help to cope with Mn stress. The global DNA methylation level in C. ambrosioides increased under Mn stress, especially in the Mn-sensitive type. Dozens of methylated loci were significantly associated with the Mn accumulation trait of C. ambrosioides, and some critical DEGs were regulated by DNA methylation. Our study comprehensively demonstrated the Mn tolerance mechanism of C. ambrosioides for the first time, and highlighted the roles of epigenetic modification in C. ambrosioides response to Mn stress. Our findings may contribute to elucidating the adaptation mechanism of hyperaccumulator to the heavy metal toxicity.
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Chenopodium ambrosioides , Manganês , Manganês/toxicidade , Manganês/metabolismo , Transcriptoma/genética , Epigenômica , Antioxidantes/metabolismoRESUMO
Learning and studying the structure-activity relationship in the bio-enzymes is conducive to the design of nanozymes for energy and environmental application. Herein, Fe single-atom nanozymes (Fe-SANs) with Fe-N5 site, inspired by the structure of cytochromes P450 (CYPs), are developed and characterized. Similar to the CYPs, the hyperoxide can activate the Fe(III) center of Fe-SANs to generate Fe(IV)O intermediately, which can transfer oxygen to the substrate with ultrafast speed. Particularly, using the peroxymonosulfate (PMS)-activated Fe-SANs to oxidize sulfamethoxazole, a typical antibiotic contaminant, as the model hyperoxides activation reaction, the excellent activity within 284 min-1 g-1 (catalyst) mmol-1 (PMS) oxidation rate and 91.6% selectivity to the Fe(IV)O intermediate oxidation are demonstrated. More importantly, instead of promoting PMS adsorption, the axial N ligand modulates the electron structure of FeN5 SANs for the lower reaction energy barrier and promotes electron transfer to PMS to produce Fe(IV)O intermediate with high selectivity. The highlight of the axial N coordination in the nanozymes in this work provides deep insight to guide the design and development of nanozymes nearly to the bio-enzyme with excellent activity and selectivity.
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Compostos Férricos , Peróxidos , Ligantes , OxirreduçãoRESUMO
OBJECTIVES: Individuals with prior cancer diagnosis are more likely to have low muscle mass (LMM) than their cancer-free counterparts. Understanding the effects of LMM on the prognosis of cancer survivors can be clinically important. The aim of this study was to investigate whether risks for all-cause and cardiovascular disease (CVD)-specific mortality differ by status of LMM in cancer survivors and a matched cohort without cancer history. METHODS: We used cohort data from the 1999-2006 and 2011-2014 National Health and Nutrition Examination Survey. Participants included 946 adults surviving for ≥1 since cancer diagnosis and a matched cohort (by age, sex, and race) without cancer history (N = 1857). LMM was defined by appendicular lean mass and body height (men <7.26 kg/m2, women <5.45 kg/m2). Death was ascertained via the National Death Index and cause of death was assessed via International Classification of Diseases, Tenth Revision. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI) of LMM. RESULTS: The mean age of cancer survivors and matched cohort was 60.6 y (SD 15) and 60.2 y (SD 14.9), respectively. The median follow-up was 10.5 y for survivors and 10.9 y for matched cohort. Overall, 22.2% of cancer survivors and 19.7% of the matched cohort had LMM, respectively. In all, 321 survivors (33.9%) and 495 participants (26.7%) in the matched cohort died during follow-up. CVD-specific deaths were identified in 58 survivors (6.1%) and 122 participants in the matched cohort (6.6%). The multivariable Cox model suggested that LMM was positively associated with all-cause (aHR, 1.73; 95% CI, 1.31-2.29) and CVD-specific (aHR, 2.13; 95% CI, 1.14-4.00) mortality in cancer survivors. The associations between LMM and risk for all-cause (aHR, 1.24; 95% CI, 0.98-1.56) and CVD-specific (aHR, 1.21; 95% CI, 0.75-1.93) mortality were not statistically significant in the matched cohort. CONCLUSION: Cancer survivors with LMM have an increased risk for all-cause and CVD-specific mortality. This increase appears to be larger than that in counterparts without cancer history.
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Sobreviventes de Câncer , Doenças Cardiovasculares , Neoplasias , Masculino , Adulto , Humanos , Feminino , Doenças Cardiovasculares/diagnóstico , Inquéritos Nutricionais , Prognóstico , Neoplasias/complicações , Músculos , Fatores de RiscoRESUMO
OBJECTIVES: In this systematic review and meta-analysis, our aim was to explore the optimal timing of ureteric stent removal after kidney transplant. MATERIALS AND METHODS: For our analyses, we searched the Cochrane Central Register of Controlled Trials, PubMed, and Embase databases for all randomized clinical trials that evaluated the timing of stent removal after kidney transplant. Patients with early versus late stent removal were compared. RESULTS: Seven eligible studies published from 2012 to 2018, which included 1277 patients, were found to be within the scope of our study. Significant differences were shown between early versus late stent removal groups with regard to development of urinary tract infections (relative risk of 0.42; 95% CI, 0.26-0.685; P < .001). In a further subgroup analysis of incidence of urinary tract infection with consideration of heterogeneity, early stent removal was also favored (relative risk at 2 and 3 weeks of 0.36 and 0.35, respectively; P < .001 for both). However, with regard to incidence of major urologic complications, there were no significant differences between early and late stent removal (odds ratio at 2 and 3 weeks of 2.79 and 1.97, respectively; P = .18 and P = .26, respectively). There were also no significant differences between groups in risk of development of urinary leakage (odds ratio at 2 weeks of 3.02, P = .18; and relative risk at 3 weeks of 2.00, P = .27). With regard to ureteral stenosis, only 3 cases were reported in the late stent removal group. CONCLUSIONS: Our study demonstrated that early ureteral stent removal (that is, not later than 3 weeks) could significantly decrease the incidence of urinary tract infections without affecting incidence of major urological complications. We suggest that the appropriate timing of stent removal should be within 14 to 21 days.
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Transplante de Rim , Ureter , Infecções Urinárias , Remoção de Dispositivo/efeitos adversos , Feminino , Humanos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Stents/efeitos adversos , Resultado do Tratamento , Ureter/cirurgia , Infecções Urinárias/diagnóstico , Infecções Urinárias/epidemiologia , Infecções Urinárias/prevenção & controleRESUMO
The aim of the study was to explore the role and molecular mechanism of dual-specificity phosphatase 8 (DUSP8) in the drug resistance of trastuzumab in breast cancer. Real-time PCR and western blot detected the difference in expression of DUSP8 between breast cancer tissue/cells and trastuzumab-resistant tissues/cells. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of DUSP8 in breast cancer. si-DUSP8 or dusp8 overexpression vector was transiently transfected, and the effects of si-DUSP8 on apoptosis, cell viability and cell migration of drug-resistant cell lines were investigated by flow cytometry, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) and Transwell assays, and its regulation mechanism finally explored. The results showed that the expression of DUSP8 in breast cancer tissues and cells was significantly higher than in matched non-tumor tissues and cells. DUSP8 was significantly upregulated in non-responsive patients compared with patients who responded to trastuzumab. ROC analysis showed that the area under the curve was 0.732, and the diagnostic sensitivity and specificity were 64.86% and 75.76%. DUSP8 knockdown promotes apoptosis and reduces trastuzumab resistance in BT474/TR and SKBR3/TR cells by inhibiting cell migration and cell viability. Knockdown of DUSP8 increased the expression of p-p38 and p-ERK, and the regulation of DUSP8 in chemotherapy resistance of breast cancer cells may be realized by mediating mitogen-activated protein kinase (MAPK)-related signaling pathways. In conclusion, knockdown of DUSP8 expression in trastuzumab-resistant cells can inhibit cell migration and proliferation, and leads to decreased drug resistance by activating MAPK signaling pathway in trastuzumab-resistant cells.
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Neoplasias da Mama , Fosfatases de Especificidade Dupla/metabolismo , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células , Resistência a Medicamentos , Resistencia a Medicamentos Antineoplásicos , Fosfatases de Especificidade Dupla/genética , Fosfatases de Especificidade Dupla/farmacologia , Feminino , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Trastuzumab/farmacologia , Trastuzumab/uso terapêuticoRESUMO
BACKGROUND: Bladder cancer (BLCA) is a malignant urothelial carcinoma with a high mortality rate. Ferroptosis is a new type of programmed cell death and functions in suppressing tumor growth and progression. However, few studies focus on ferroptosis and BLCA. MATERIALS AND METHODS: We explored the potential oncogenic roles of ferroptosis-related genes in BLCA based on multiple public datasets. We then used univariate and multivariate cox regression to build a new survival model based on ferroptosis-related genes to predict the survival of BLCA. RESULTS: We found that 23 ferroptosis-related genes had a strong correlation with each other in BLCA. Eight ferroptosis-related genes, CDKN1A, HSPA5, NFE2L2, MT1G, FANCD2, CISD1, TFRC, NCOA4, had a significantly different expression and heat-map. HSPA5 and CISD1 have a statistically significant difference in OS and DFS. Besides, CISD1 had an ideal nomogram to predict the 1-3-5-year OS (C-index: 0.701, Pâ¯<â¯.001). Furthermore, HSPA5 and CISD1 had a lower DNA methylation rate than normal tissue and HSPA5 had a positive connection with TMB (Pâ¯=â¯.02). In addition, HSPA5 participated in the DNA replication and P53 signaling pathway, and CISD1 mediated the oxidative phosphorylation and positive regulation of the intrinsic apoptotic signaling pathway. CONCLUSION: Ferroptosis-related genes had a strong correlation with BLCA, notably, HSPA5 and CISD1 may play a role in inducing ferroptosis to suppress bladder tumorigenesis and CISD1 can be a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.
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Carcinoma de Células de Transição , Ferroptose , Neoplasias da Bexiga Urinária , Biomarcadores , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Methylation has a close relationship with immune reactions, metastasis, and cancer cell growth. Additionally, RNA methylation-related proteins have emerged as potential cancer therapeutic targets. The connection between the tumor microenvironment (TME) and methylation-related genes (MRGs) remains unclear. We explored the expression patterns of the MRGs in the genome and transcriptional fields of 796 prostate cancer (PCa) samples using two separate data sets. We identified a relationship between patient clinicopathological characteristics, prognosis, TME cell infiltrating qualities, and different MRG changes, as well as the identification of two distinct molecular groupings. Then, we formed an MRGs model to predict overall survival (OS), and we tested the accuracy of the model in patients with PCa. In addition, we developed a very accurate nomogram to improve the MRG model's clinical applicability. The low-risk group had fewer tumor mutational burden (TMB), greater tumor immune dysfunction and exclusion (TIDE) ratings, fewer mutant genes, and better OS prospects. We discuss how MGRs may affect the prognosis, clinically important traits, TME, and immunotherapy responsiveness in PCa. In order to get a better understanding of MRGs in PCa, we could further explore the prognosis and create more effective immunotherapy regimens to open new avenues.
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Background: Bladder carcinoma is a common malignancy of the urinary system. The previous study showed that EPDR1 expression was significantly related to the carcinogenesis and progression of bladder carcinoma. Methods: We retrospectively reviewed the records of 621 patients who were newly diagnosed with bladder carcinoma between January 2018 and August 2020 at The Affiliated Hospital of Zunyi Medical University. We conducted immunohistochemistry of EPDR1 in tumor tissues. Meanwhile, tumor budding evaluation was also carried out by 2 independent experienced pathologists. Results: 80 patients were included in this study with a median age of 66 years (range; 42-88 years). 45% of the patients (36/80) were non-muscle-invasive bladder carcinoma patients, while 55% of muscle-invasive bladder carcinoma(44/80). The follow-up time was from 6 months to 36 months. We found that there were significant differences in expression of EPDR1 in the tumor pT stages(p<0.05), pM stages(p<0.05), and pN stages(p<0.05). Meanwhile, a higher expression of EPDR1 indicated a worse outcome for the patient(p<0.05). A tendency toward a worse status of the patient was accompanied by a high positive rate (p<0.001). Moreover, the IOD of EPDR1 had a positive relationship with TB (p<0.05). Furthermore, we found that EPDR1 and tumor budding could be crucial factors for affecting the prognosis of bladder carcinoma, even better than pTMN(Riskscore=(0.724)* pT_stage +(4.960) *EPDR1+(4.312)*TB). Conclusion: In conclusion, bladder cancer patients with higher expression levels of EPDR1 had worse survival outcomes. The combination of TB and EPDR1 levels could predict the prognosis for muscle-invasive bladder cancer patients.