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Aflatoxin B1 (AFB1), a potent mycotoxin, is one of the environmental risk factors that cause liver cancer. In the liver, the bioactivated AFB1 intercalates into the DNA double helix to form a bulky DNA adduct which will lead to mutation if left unrepaired. Here, we adapted the tXR-seq method to measure the nucleotide excision repair of AFB1-induced DNA adducts at single-nucleotide resolution on a genome-wide scale, and compared it with repair data obtained from conventional UV-damage XR-seq. Our results showed that transcription-coupled repair plays a major role in the damage removal process. We further analyzed the distribution of nucleotide excision repair sites for AFB1-induced DNA adducts within the 3D human genome organization. Our analysis revealed a heterogeneous AFB1-dG repair across four different organization levels, including chromosome territories, A/B compartments, TADs, and chromatin loops. We found that chromosomes positioned closer to the nuclear center and regions within A compartments have higher levels of nucleotide excision repair. Notably, we observed high repair activity around both TAD boundaries and loop anchors. These findings provide insights into the complex interplay between AFB1-induced DNA damage repair, transcription, and 3D genome organization, shedding light on the mechanisms underlying AFB1-induced mutagenesis.
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OBJECTIVE: To better understand how to clear cell renal cell cancer (ccRCC) is affected by the regulator of G protein signaling-1 (RGS1), its effect on immune infiltration, macrophage polarization, tumor proliferation migration, and to explore whether RGS1 may serve as a marker and therapeutic target for ccRCC. PATIENTS AND METHODS: In this study, a total of 20 surgical specimens of patients with pathological diagnosis of ccRCC admitted to the Department of Urology of the Second Affiliated Hospital of Anhui Medical University from November 2021 to June 2022 were selected for pathological and protein testing, while the expression of RGS1 in tumors, immune infiltration, and macrophage polarization, particularly M2 macrophage linked to the development of tumor microenvironment (TME), were combined with TGCA database and GO analysis. We also further explored and studied the expression and function of RGS1 in TME, investigated how RGS1 affected tumor growth, migration, apoptosis, and other traits, and initially explored the signaling pathways and mechanisms that RGS1 may affect. RESULTS: RGS1 was found to be expressed at higher quantities in ccRCC than in normal cells or tissues, according to bioinformatics analysis and preliminary experimental data from this work. Using the TCGA database and GO analysis to describe the expression of RGS1 in a range of tumors, it was found that ccRCC had a much higher level of RGS1 expression than other tumor types. The results of gene enrichment analysis indicated that overexpression of RGS1 may be associated with immune infiltration. The outcomes of in vitro tests revealed that RGS1 overexpression in ccRCC did not significantly alter the proliferation and migration ability of ccRCC, but RGS1 overexpression promoted apoptosis in ccRCC. By in vitro co-culture experiments, RGS1 overexpression inhibited M2 macrophage polarization and also suppressed the Jagged-1/Notch signaling pathway. CONCLUSIONS: RGS1 is highly expressed in ccRCC, while overexpression of RGS1 may increase immune infiltration in the TME and reduce the polarization of M2 macrophages while promoting apoptosis in ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Transducción de Señal , Macrófagos , Neoplasias Renales/genética , Proteínas de Unión al GTP , Microambiente TumoralRESUMEN
BACKGROUND: This study aimed to compare the clinical outcomes of patients who underwent three-port laparoscopic radical cystectomy (LRC) with orthotopic neobladder (ONB) and traditional five-port method. METHODS: From January 2017 to November 2020, 100 patients underwent LRC + ONB at a third-level grade A hospital. RESULTS: Our study included 55 patients who underwent three-port LRC and 45 patients who underwent the five-port method. There were no significant differences in perioperative data such as operation time (253.00 ± 43.89 vs. 259.07 ± 52.31 min, P = 0.530), estimated blood loss (EBL)(97.64 ± 59.44 vs. 106.67 ± 55.35 min, P = 0.438), day to flatus (2.25 ± 1.49 vs. 2.76 ± 1.77 days, P = 0.128), day to regular diet (7.07 ± 2.99 vs. 7.96 ± 3.32 days, P = 0.165), day to pelvic drain removal (9.58 ± 3.25 vs. 10.53 ± 3.80 days, P = 0.180), and hospital stay after operation (11.62 ± 3.72 vs. 11.84 ± 4.37 days, P = 0.780) between the two groups. The only significant difference was in the treatment cost (P = 0.035). Similarly, postoperative complications, quality of life, and tumor outcomes were not significantly different between the two groups (P > 0.05). CONCLUSIONS: The three-port method is safe and feasible for patients suitable for traditional five-port LRC with an orthotopic neobladder.
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Laparoscopía , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/métodos , Estudios Retrospectivos , Calidad de Vida , Resultado del Tratamiento , Laparoscopía/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Three-dimensional (3D) printing technology involves the application of digital models to create 3D objects. It is used in construction and manufacturing and has gradually spread to medical applications, such as implants, drug development, medical devices, prosthetic limbs, and in vitro models. The application of 3D printing has great prospects for development in orthopedics, maxillofacial plastic surgery, cardiovascular conditions, liver disease, and other fields. With in-depth research on 3D printing technology and the continuous update of printing materials, this technology also shows broad development prospects in renal medicine. In this paper, the author mainly summarizes the basic theory of 3D printing technology, its research progress, application status, and development prospect in renal diseases.
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Clear cell renal cell carcinoma is a common malignant tumor of the urinary system. The mechanism of its occurrence and development is unknown, and there is currently few effective comprehensive predictive markers for prognosis and treatment response. With the discovery of a new cell death process - cuproptosis drew the attention of researchers. We constructed a model for the prediction of clinical prognosis and immunotherapy response through integrative analysis of gene expression datasets from KIRC samples in The Cancer Genome Atlas (TCGA) database. During the course of the study, we found that cuproptosis genes are significantly differentially expressed between clear cell renal cell carcinoma samples and normal samples. Based on this, we put forward the prognostic model for cuproptosis gene related-long non-coding RNA. And through various statistic and external independent cohorts, we proved that the model is accurate and stable, worthy of clinical application and further exploration and validation.
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Apoptosis , Carcinoma de Células Renales , Neoplasias Renales , ARN Largo no Codificante , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/patología , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/patología , ARN Largo no Codificante/genética , CobreRESUMEN
Renal cell carcinoma (RCC), as one of the most common urological malignancies, has many histologic and molecular subtypes, among which clear cell renal cell carcinoma (ccRCC) is one of the most common causes of tumor-related deaths. However, the molecular mechanism of ccRCC remains unclear. In order to identify the candidate genes that may exist in the occurrence and development of ccRCC, microarray datasets GSE6344, GSE16441, GSE36895, GSE53757 and GSE76351 had been downloaded from Gene Expression Omnibus (GEO) database. Apart from that, the differentially expressed genes (DEGs) were screened through Bioinformatics & Evolutionary Genomics. In addition, the protein-protein interaction network (PPI) was constructed, and the module analysis was performed using STRING and Cytoscape. By virtue of DAVID online database, GO/KEGG enrichment analysis of DEGs was performed. Consequently, a total of 118 DEGs were screened, including 24 up-regulated genes and 94 down-regulated genes. The plug-in MCODE of Cytoscape was adopted to analyze the most significant modules of DEGs. What's more, the genes with degree greater than 10 in DEGs were selected as the hub genes. The overall survival (OS) and disease progression free survival (DFS) of 9 hub genes were analyzed through GEPIA2 online platform. As shown by the survival analysis, SLC34A1, SLC12A3, SLC12A1, PLG, and ENO2 were closely related to the OS of ccRCC, whereas SLC34A1 and LOX were closely related to DFS. Among 11 SLC members, 6 SLC members were highly expressed in non-cancerous tissues (SLC5A2, SLC12A1, SLC12A3, SLC34A1, SLC34A2, SLC34A3). Besides, SLC12A5 and SLC12A7 were highly expressed in ccRCC. Furthermore, SLC12A1-A7, SLC34A1 and SLC34A3 were closely related to OS, whereas SLC12A2/A4/A6/A7 and SLC34A1/A3 were closely related to DFS. In addition, 5 algorithms were used to analyze hub genes, the overlapping genes were AQP2 and KCNJ1. To sum up, hub gene can help us understand the molecular mechanism of the occurrence and development of ccRCC, thereby providing a theoretical basis for the diagnosis and targeted therapy of ccRCC.
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BACKGROUND: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and has a poor prognosis. RBR E3 ubiquitin ligases are a special class of E3 ubiquitin ligases which contain three zinc-bing domains that catalyze ubiquitin to substrate proteins. The RBR family of E3 ubiquitin ligases has been reported in various human malignancies, but the roles of RBR E3 ubiquitin ligases in LUAD remain unclear. METHODS: By using TCGA and Kaplan-Meier plotter databases, we examined the expression and prognostic value of RBR E3 ubiquitin ligases. cBioPortal was used to analyze genetic mutations. The STRING database was used to build a protein interactive network. GO, KEGG, and GSEA were performed to investigate the potential biological functions of RBR E3 ubiquitin ligases. RESULTS: The expression of ARIH2, RNF144B, RNF216, and RNF217 was significantly related to the clinicopathological parameters and prognosis in LUAD patients. GSEA enrichment result showed ARIH2, RNF144B, RNF216, and RNF217 were all associated with NADH dehydrogenase complex assembly. GO functional enrichment analysis revealed that four RBR E3 ubiquitin ligases and their interactors were most correlated with ubiquitin-protein transferase activity. KEGG pathway analysis indicated they were associated with cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway and NF-kappa B signaling pathway. CONCLUSIONS: Our comprehensive bioinformatic analysis revealed that ARIH2, RNF144B, RNF216, and RNF217 may be new prognostic biomarkers and these findings will help to better understand the distinct roles of RBR E3 ubiquitin ligases in LUAD.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Humanos , Neoplasias Pulmonares/genética , Pronóstico , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinasRESUMEN
As one of the common malignancies in the urinary system, kidney cancer has been receiving explorations with respect to its pathogenesis, treatment and prognosis due to its high morbidity, high mortality and low drug efficiency. Such epigenetic modifications for RNA molecules as N6-methyladenosine (m6A) usher in another perspective for the research on tumor mechanisms, and an increasing number of biological processes and prognostic markers have been revealed. In this study, the transcriptome data, clinical data and mutation spectrum data of KIRC in the TCGA database were adopted to construct an m6A-related lncRNA prognostic model. Besides, the predictive ability of this model for clinical prognosis was evaluated, and some compounds sensitive to therapies for KIRC were screened. The findings of this study demonstrate that this effective and stable model has certain clinical application value.
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BACKGROUND: Runt-related transcription factor 1 (RUNX1) is a vital regulator of mammalian expression. Despite multiple pieces of evidence indicating that dysregulation of RUNX1 is a common phenomenon in human cancers, there is no evidence from pan-cancer analysis. METHODS: We comprehensively investigated the effect of RUNX1 expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases, including Gent2, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), the Human Protein Atlas (HPA), UALCAN, PrognoScan, cBioPortal, STRING, and Metascape. RESULTS: Bioinformatics data indicated that RUNX1 was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer. Immunohistochemical results showed that most cancer tissues were moderately positive for granular cytoplasm, and RUNX1 was expressed at a medium level in four types of tumors, including cervical cancer, colorectal cancer, glioma, and renal cancer. RUNX1 expression was positively correlated with infiltrating levels of cancer-associated fibroblasts (CAFs) in 33 different cancers. Moreover, RUNX1 expression may influence patient prognosis by activating oncogenic signaling pathways in human cancers. CONCLUSION: Our findings suggest that RUNX1 expression correlates with patient outcomes and immune infiltrate levels of CAFs in multiple tumors. Additionally, the increased level of RUNX1 was linked to the activation of oncogenic signaling pathways in human cancers, suggesting a potential role of RUNX1 among cancer therapeutic targets. These findings suggest that RUNX1 can function as a potential prognostic biomarker and reflect the levels of immune infiltrates of CAFs in human cancers.
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Fibroblastos Asociados al Cáncer , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Neoplasias , Biomarcadores de Tumor/genética , Fibroblastos Asociados al Cáncer/metabolismo , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , PronósticoRESUMEN
Treacle ribosome biogenesis factor 1 (TCOF1) is a nucleolar factor that regulates ribosomal DNA (rDNA) transcription in the nucleolus. TCOF1 has been previously reported to be implicated in Treacher Collins-Franceschetti syndrome (TCS), a congenital disorder of craniofacial development. Except TCS, TCOF1 has not been reported to be involved in other diseases so far. Here, we show that TCOF1 expression is aberrantly elevated in human hepatocellular carcinoma (HCC) and correlates with HCC progression and poor outcome. In vitro and in vivo studies reveal oncogenic roles of TCOF1 in HCC. Mechanistically, TCOF1 regulates KRAS-activated genes and epithelial-mesenchymal transition (EMT) genes in HCC and is required for the increased ribosomal RNA (rRNA) production, a hallmark of cancer. Interestingly, our analysis reveals an inverse correlation between TCOF1 expression and tumor infiltration of antitumor immune cells, suggesting that TCOF1 may also have an important impact on antitumor immune responses in HCC. Together, our findings support a model in which TCOF1 coordinates oncogenic activation and rRNA production to promote HCC tumorigenesis. The inverse correlation between TCOF1 expression and the infiltration of antitumor immune cells opens a new avenue to understanding the promoting role of TCOF in HCC tumorigenesis.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , ARN Ribosómico/metabolismo , Animales , Apoptosis , Carcinogénesis , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Linfocitos Infiltrantes de Tumor , Ratones , Proteínas Nucleares/genética , Fosfoproteínas/genética , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , ARN Ribosómico/genética , Transcripción GenéticaRESUMEN
C/EBPß is a member of the CCAAT/enhancer-binding protein (C/EBP) family, which consists of a number of b-ZIP transcription factors. Although C/EBPß has been implicated in the development of certain cancers, including breast cancer, it remains unknown whether dysregulation of C/EBPß in breast cancer is subtype-specific. Moreover, the underlying mechanisms by which C/EBPß regulates breast cancer carcinogenesis are not fully understood. Here, we present evidence that C/EBPß is specifically overexpressed in human TNBC samples, but not in non-TNBC samples. C/EBPß depletion dramatically suppressed TNBC cell growth, migration, invasion, and colony formation ability. A subsequent mechanistic study revealed that the JAK/STAT signaling pathway was upregulated in C/EBPß_high TNBC samples compared with C/EBPß_low TNBC samples. C/EBPß ChIP-seq and qPCR were performed to demonstrate that C/EBPß directly binds to and regulates JAK/STAT signaling pathway genes in TNBC. Taken together, our data indicate the oncogenic role of C/EBPß in human TNBC and reveal a novel mechanism by which C/EBPß promotes TNBC carcinogenesis.
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Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Neoplasias de la Mama Triple Negativas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Células Madre Neoplásicas , Neoplasias de la Mama Triple Negativas/etiología , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUNDS: The NuRD (Nucleosome Remodeling and Deacetylation) complex is a repressive complex in gene transcription by modulating chromatin accessibility of target genes to transcription factors and RNA polymerase II. Although individual subunits of the complex have been implicated in many other cancer types, the complex's role in human hepatocellular carcinoma (HCC) is not fully understood. More importantly, the NuRD complex has not yet been investigated as a whole in cancers. METHODS: We analyzed the expression of the NuRD complex in HCC and evaluated the prognostic value of NuRD complex expression in HCC using the RNA-seq data obtained from the TCGA project. We examined the effect of CHD4 knockdown on HCC cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition, colony-forming ability, and on complement gene expression. We also performed bioinformatic analyses to investigate the correlation between the NuRD complex expression and immune infiltration. RESULTS: We found that nine subunits, out of 14 subunits of the NuRD complex examined, were significantly overexpressed in HCC, and their expression levels were positively correlated with cancer progression. More importantly, our data also demonstrated that these subunits tended to be overexpressed as a whole in HCC. Subsequent studies demonstrated that knockdown of CHD4 in HCC cells inhibits cell proliferation, migration, invasion, and colony-forming ability and promotes apoptosis of HCC cells, indicating that the CHD4/NuRD complex plays oncogenic roles in HCC. Further analysis revealed that the CHD4/NuRD complex regulates complement gene expression in HCC. Intriguingly, we found that the CHD4/NuRD complex expression was inversely correlated with CD8 T cell infiltration in HCC. CONCLUSIONS: Our data demonstrate that the CHD4/NuRD complex plays an oncogenic role in human HCC and regulates complement gene expression in HCC cells. The results of inverse correlation between the CHD4/NuRD complex and CD8 T cell and DC cell infiltration in HCC suggest that the CHD4/NuRD complex not only plays direct regulatory roles in HCC cells, but also has an impact on the immune microenvironment of HCC.