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1.
Methods Mol Biol ; 2558: 63-74, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36169856

RESUMO

The covalently bound FAD cofactor in monoamine oxidase (MAO) is reduced by the amine substrate and reoxidized by oxygen. Visible spectroscopy provides a convenient tool to study the interaction of ligands and the kinetics of the half-reactions for mechanistic investigations. Equilibrium redox titrations allow measurement of redox potentials, while rapid mixing experiments allow determination of the rate of reduction by different substrates and of covalent adduct formation by irreversible inactivators. Three techniques are described: (1) measuring ligand interactions by alterations in the spectrum, especially at 495 nm; (2) reducing MAO, including the essentials for anaerobic procedures; and (3) studying kinetics of reduction, reoxidation, or inactivation of MAO.


Assuntos
Flavina-Adenina Dinucleotídeo , Monoaminoxidase , Aminas , Flavina-Adenina Dinucleotídeo/metabolismo , Cinética , Ligantes , Monoaminoxidase/metabolismo , Oxirredução , Oxigênio , Análise Espectral
2.
Methods Mol Biol ; 2558: 75-96, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36169857

RESUMO

Designed to measure binding interactions between small molecules and receptor proteins, radioligand binding approaches may also be applied to interactions between monoamine oxidase (MAO) and its ligands. The technique may be used with tissue homogenates or with mitochondrial membranes and can provide information about binding site density, ligand affinity, binding rate constants, and binding events at sites that do not impact absorbance characteristics of the flavin cofactor and that may not be amenable to spectrophotometric studies. This overview describes the use of a cell harvester in a common filtration approach to measure binding to MAO of radiolabeled substrates, inhibitors, or allosteric ligands in saturation analyses and to take advantage of the principles of competition to obtain quantitative binding data for unlabeled ligands that may bind with much lower affinity. The quality and reproducibility of data are impacted by factors such as choice of ligand concentrations, pipetting technique, graphing and regression approaches, and scintillation counting parameters, and consideration is given to these and other factors that may influence the results.


Assuntos
Inibidores da Monoaminoxidase , Monoaminoxidase , Sítios de Ligação , Flavinas/metabolismo , Ligantes , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Ensaio Radioligante , Reprodutibilidade dos Testes
3.
Methods Mol Biol ; 2576: 95-109, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152179

RESUMO

Type-1 cannabinoid receptor (CB1), one of the main targets of endocannabinoids, plays a key role in several pathophysiological conditions that affect both the central nervous system and peripheral tissues. Today, its biochemical identification and pharmacological characterization, as well as the screening of thousands of novel ligands that might be useful for developing CB1-based therapies, are the subject of intense research. Among available techniques that allow the analysis of CB1 binding activity, radioligand-based assays represent one of the best, fast, and reliable methods.Here, we describe radioligand binding methods standardized in our laboratory to assess CB1 binding in both tissues and cultured cells. We also report a high-throughput radioligand binding assay that allows to evaluate efficacy and potency of different compounds, which might represent the basis for the development of new drugs that target CB1-dependent human diseases.


Assuntos
Endocanabinoides , Receptor CB2 de Canabinoide , Humanos , Ligantes , Ligação Proteica , Ensaio Radioligante , Receptores de Canabinoides
4.
Methods Mol Biol ; 2576: 119-131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152181

RESUMO

The transient receptor potential vanilloid 1 ion channel (TRPV1) is a ligand-gated nonselective calcium-permeant cation channel involved in the detection of a wide variety of chemical and physical noxious stimuli, ranging from exogenous and endogenous ligands to noxious heat (>42 °C) and low pH (pH < 5.2). Due to its central role in pain and hyperalgesia, TRPV1 is considered a relevant therapeutic target for the development of analgesic and anti-inflammatory drugs potentially useful to relieve chronic, neuropathic, and inflammatory pain and to treat disorders such as inflammatory bowel disease. In this view, the availability of in vitro assays for the screening of novel TRPV1 modulators is highly desirable. Since TRPV1 activation leads to an increase in the intracellular calcium (Ca2+) levels, the use of Ca2+ fluorescent indicators represent a valuable and sensitive tool for monitoring such intracellular changes. In this chapter, we describe methods for recording and monitoring Ca2+ signals through the fluorescent indicators Fluo-4 acetoxymethyl (AM) and Fura-2 AM in HEK-293 cells transfected with TRPV1 or other thermoTRP channels.


Assuntos
Canais de Potencial de Receptor Transitório , Analgésicos , Cálcio/metabolismo , Capsaicina , Cátions , Fluorescência , Fura-2 , Células HEK293 , Humanos , Ligantes , Dor/tratamento farmacológico , Canais de Cátion TRPV/fisiologia
5.
Methods Mol Biol ; 2576: 145-153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152183

RESUMO

Peroxisome proliferator-activated receptors (PPARs) have been exploited as drug targets for combating multiple diseases. Several activators with different selectivity for the PPAR α, γ, and δ subtypes have been introduced into the market or have reached advanced clinical trials. Binding assays are of utmost importance for the discovery and profiling of such PPAR ligands. Binding assays are often based on radioligands, in particular, tritiated molecules are applied. We developed synthetic procedures for tritiating various PPAR agonists and applied these radioligands for setting up a scintillation proximity assay (SPA) for PPAR α, γ, and δ. These SPAs allow to assess the binding affinities of PPAR α, γ, and δ ligands, along with their respective subtype selectivity profiles. Therefore, SPA is an important tool for hit discovery and lead optimization campaigns aimed at identifying next-generation PPAR ligands.


Assuntos
PPAR alfa , PPAR delta , Hipoglicemiantes , Ligantes , PPAR alfa/agonistas , PPAR alfa/metabolismo , PPAR delta/agonistas , PPAR delta/metabolismo , PPAR gama/metabolismo , Receptores Ativados por Proliferador de Peroxissomo
6.
Methods Mol Biol ; 2576: 171-179, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152185

RESUMO

The cyclic AMP assay is a functional assay that is commonly used to determine the pharmacological behavior (agonists, antagonists, and inverse agonists) of G-protein coupled receptor ligands. Here, we describe the cyclic AMP assay that is carried out with commercially available nonradioligand ready-to-use kits and CHO (Chinese Hamster Ovarian) cells stably transfected with the human cannabinoid CB2 receptor.


Assuntos
Canabinoides , AMP Cíclico , Animais , Células CHO , Cricetinae , Cricetulus , Humanos , Ligantes , Receptor CB2 de Canabinoide/genética , Receptores de Canabinoides
7.
Methods Mol Biol ; 2576: 189-199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152187

RESUMO

Cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R) are G protein-coupled receptors (GPCRs) that activate a variety of pathways upon activation by (partial) agonists including the G protein pathway and the recruitment of ß-arrestins. Differences in the activation level of these pathways lead to biased signaling. Here, we describe a detailed protocol to characterize the potency and efficacy of ligands to induce or inhibit ß-arrestin recruitment to the human CB1R and CB2R using the PathHunter® assay. This is a cellular assay that uses a ß-galactosidase complementation system which has a chemiluminescent read-out and can be performed in 384-well plates. We have successfully used this assay to characterize a set of reference ligands (both agonists, antagonists, and an inverse agonist) on human CB1R and CB2R, of which some examples will be presented here.


Assuntos
Proteínas de Ligação ao GTP , Receptores Acoplados a Proteínas G , Proteínas de Ligação ao GTP/metabolismo , Humanos , Ligantes , Receptores de Canabinoides/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestina 1/metabolismo , beta-Arrestinas/metabolismo , beta-Galactosidase/metabolismo
8.
Methods Mol Biol ; 2576: 395-406, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152205

RESUMO

Measuring the functional behavior of G protein-coupled receptors (GPCRs) has been a major focus of academic and pharmaceutical research for many decades. These efforts have led to the development of many assays to measure the downstream effects of ligand binding on receptor activity. In this chapter, we describe an internalization/recycling assay that can be used to track changes in receptor number at the plasma membrane. Used in concert with other assays, this antibody-based technique can provide dynamic information on GPCR activation by receptor-specific ligands.


Assuntos
Proteínas de Ligação ao GTP , Receptores Acoplados a Proteínas G , Membrana Celular/metabolismo , Células Cultivadas , Proteínas de Ligação ao GTP/metabolismo , Ligantes , Receptores Acoplados a Proteínas G/metabolismo
9.
Methods Mol Biol ; 2576: 495-504, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152212

RESUMO

A screening pool consisting of 617710 drug-like query molecules properly filtered from the ChEMBL database was employed for a ligand-based reverse screening toward the type 2 cannabinoid receptor (CB2) target. By using our recently developed PLATO polypharmacological web platform, 233 out of 617710 drug-like molecules were prioritized on the basis of the predicted bioactivity values, better than 0.2 µM with a probability of about 98%, toward the CB2 target. Building on these results, the occurrence of putative CB2-related targets was also investigated for prospective repurposing studies.


Assuntos
Polifarmacologia , Receptor CB2 de Canabinoide , Ligantes , Estudos Prospectivos , Receptores de Canabinoides
10.
Methods Mol Biol ; 2576: 477-493, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152211

RESUMO

Computational methods in medicinal chemistry facilitate drug discovery and design. In particular, machine learning methodologies have recently gained increasing attention. This chapter provides a structured overview of the current state of computational chemistry and its applications for the interrogation of the endocannabinoid system (ECS), highlighting methods in structure-based drug design, virtual screening, ligand-based quantitative structure-activity relationship (QSAR) modeling, and de novo molecular design. We emphasize emerging methods in machine learning and anticipate a forecast of future opportunities of computational medicinal chemistry for the ECS.


Assuntos
Química Computacional , Endocanabinoides , Desenho de Fármacos , Ligantes , Aprendizado de Máquina , Relação Quantitativa Estrutura-Atividade
11.
Methods Mol Biol ; 2578: 249-257, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152293

RESUMO

Analytical platforms for small extracellular vesicle (sEV) high-throughput analysis are highly desirable. These bionanoparticles present fairly distinctive lipid membrane features including high curvature, lipid-packing defects, and a relative abundance in lipids. sEV membrane could be considered as a "universal" marker, complementary or alternative to traditional surface-associated proteins. Here, we describe the use of membrane-sensing peptides as a new, highly efficient ligand to directly integrate sEV capturing and analysis on a microarray platform.


Assuntos
Vesículas Extracelulares , Peptídeos , Vesículas Extracelulares/metabolismo , Ligantes , Lipídeos , Proteínas de Membrana/metabolismo , Membranas/metabolismo , Peptídeos/metabolismo
12.
Methods Mol Biol ; 2570: 3-11, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156770

RESUMO

The systematic evolution of ligands by exponential enrichment (SELEX) enables the identification of ssDNA or RNA sequences binding to different target molecules, highly specific and with high affinity. In this chapter, we describe a selection strategy with ssDNA for a histidine-tagged protein that could be either performed hands-on manually or fully automated by an appropriate robotic selection platform.


Assuntos
Aptâmeros de Nucleotídeos , Técnica de Seleção de Aptâmeros , Aptâmeros de Nucleotídeos/química , DNA de Cadeia Simples/genética , Histidina/genética , Ligantes , Proteínas/genética
13.
Methods Mol Biol ; 2570: 13-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156771

RESUMO

Oligonucleotide ligands (DNA, RNA, or XNA), also known as aptamers, are selected against various target molecules using an iterative, evolutionary process called systematic evolution of ligands by exponential enrichment (SELEX). To select aptamers against complex cell surface proteins in their native state, a variant of SELEX termed ligand-guided selection (LIGS) was recently introduced. The significance of LIGS is rooted in its strategy of exploiting the selection step in SELEX to identify highly specific aptamers against known cell surface markers. Thus, in LIGS, a higher-affinity secondary ligand, such as a monoclonal antibody (mAb) to a whole-cell bound to an evolved SELEX library, is introduced to outcompete sequences against the mAb targeting cell surface protein or induce a conformational switch to destabilize the aptamer-surface cell surface protein resulting in elution of the sequences. Here, we describe the detailed method of LIGS utilized in identifying aptamers against T-cell receptor cluster of differentiation three complex (TCR-CD3) expressed in human T-cells and T-cell leukemia.


Assuntos
Aptâmeros de Nucleotídeos , Técnica de Seleção de Aptâmeros , Anticorpos Monoclonais , Aptâmeros de Nucleotídeos/genética , Aptâmeros de Nucleotídeos/metabolismo , Humanos , Ligantes , RNA , Receptores de Antígenos de Linfócitos T , Técnica de Seleção de Aptâmeros/métodos
14.
Methods Mol Biol ; 2570: 63-71, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156774

RESUMO

SELEX has enabled the selection of aptamers, nucleic acids that can bind a defined ligand, in some cases with exceptionally high affinity and specificity. The SELEX protocol has been adapted many times to fit a variety of needs. This protocol describes such an adaptation, namely, RNA-Capture SELEX that we have used to successfully develop small molecule-binding RNA aptamers. Our proposed method specifically selects not only for excellent binding but also for conformational switching. In consequence, we found this SELEX method to be particularly suitable for identifying aptamers for further application in synthetic riboswitch engineering.


Assuntos
Aptâmeros de Nucleotídeos , Riboswitch , Aptâmeros de Nucleotídeos/química , Ligantes , Fenômenos Magnéticos , RNA , Técnica de Seleção de Aptâmeros/métodos , Estreptavidina/metabolismo
15.
Methods Mol Biol ; 2570: 105-118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156777

RESUMO

Isothermal titration calorimetry (ITC) is a technique where the heat given off, or absorbed, during a binding event is measured and used to determine the binding thermodynamics and affinity associated with binding. This protocol focuses on ITC applications for studying aptamer interactions with small molecule ligands where ITC has the advantage of being a label-free solution-based technique. The limitation of ITC using a relatively large amount of material compared to other analytical techniques is not applicable here as large amounts of nucleic acids, especially DNA, can be readily obtained. In this chapter we describe how to use ITC methods to measure the thermodynamics and affinity of binding using the interaction of quinine with a DNA cocaine-binding aptamer as an example.


Assuntos
Aptâmeros de Nucleotídeos , Cocaína , Ácidos Nucleicos , Aptâmeros de Nucleotídeos/química , Calorimetria/métodos , Cocaína/química , Ligantes , Ácidos Nucleicos/metabolismo , Ligação Proteica , Quinina/química , Termodinâmica
16.
Methods Mol Biol ; 2570: 129-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156779

RESUMO

The quantitative characterization of aptamer-ligand interactions is an important step in the aptamer development process. However, certain pitfalls impede KD determination, especially when working with small molecule ligands. These include altered binding behavior caused by ligand immobilization. Further, the compulsory requirement for major differences in size between the bound and unbound state makes small molecule ligands ineligible for separation-based methods. MicroScale Thermophoresis circumvents such limitations as binding is accurately quantified with both binding partners free in solution and independent of ligand size. In this chapter, we present a protocol for the characterization of a DNA aptamer binding to its small molecule ligand daunorubicin.


Assuntos
Aptâmeros de Nucleotídeos , Aptâmeros de Nucleotídeos/química , Daunorrubicina , Ligantes , Ligação Proteica
17.
Methods Mol Biol ; 2570: 155-173, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156781

RESUMO

Fluorogenic RNA aptamers are synthetic RNAs that have been evolved by in vitro selection methods to bind and light up conditionally fluorescent organic ligands. Compared with other probes for RNA detection, they are less invasive than hybridization-based methods (FISH, molecular beacons) and are considerably smaller than fluorescent protein-recruiting systems (MS2, Pumilio variants). Fluorogenic aptamers have therefore found widespread use as genetically encodable tags for RNA detection in live cells and have also been used in combination with riboswitches to construct versatile metabolite sensors for in vitro use. Their success builds on a fundamental understanding of their three-dimensional structure to explain the mechanisms of ligand interaction and to rationally design functional aptamer devices. In this protocol, we describe a supramolecular FRET-based structure probing method for fluorogenic aptamers that exploits distance- and orientation-dependent energy transfer efficiencies between site-specifically incorporated fluorescent nucleoside analogs and non-covalently bound ligands, exemplified by 4-cyanoindol riboside (4CI) and the DMHBI+-binding RNA aptamer Chili. This method yields structural restraints that bridge the gap between traditional low-resolution secondary structure probing methods and more elaborate high-resolution methods such as X-ray crystallography and NMR spectroscopy.


Assuntos
Aptâmeros de Nucleotídeos , Riboswitch , Aptâmeros de Nucleotídeos/química , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Ligantes , Nucleosídeos , RNA/genética
18.
Methods Mol Biol ; 2570: 243-269, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156788

RESUMO

Small-molecule sensing is a major issue as they can serve both in fundamental science and as makers of various diseases, contaminations, or even environment pollution. RNA aptamers are single-stranded nucleic acids that can adopt different conformations and specifically recognize a wide range of ligands, making them good candidates to develop biosensors of small molecules. Recently, light-up RNA aptamers have been introduced and used as starting building blocks of RNA-based fluorogenic biosensors. They are typically made of three domains: a reporter domain (a light-up aptamer), connected to a sensor domain (another aptamer) via a communication module. The latter is instrumental as being in charge of information transmission between the sensor and the reporting domains. Here we present an ultrahigh-throughput screening procedure to develop RNA-based fluorogenic biosensors by selecting optimized communication modules through an exhaustive functional exploration of every possible sequence permutation using droplet-based microfluidics and next-generation sequencing.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Aptâmeros de Nucleotídeos/genética , Técnicas Biossensoriais/métodos , Ligantes , Microfluídica/métodos , RNA/genética
19.
J Nanobiotechnology ; 20(1): 425, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153589

RESUMO

BACKGROUND: Poor in vivo targeting of tumors by chemotherapeutic drugs reduces their anti-cancer efficacy in the clinic. The discovery of over-expressed components on the tumor cell surface and their specific ligands provide a basis for targeting tumor cells. However, the differences in the expression levels of these receptors on the tumor cell surface limit the clinical application of anti-tumor preparations modified by a single ligand. Meanwhile, toxicity of chemotherapeutic drugs leads to poor tolerance to anti-tumor therapy. The discovery of natural active products antagonizing these toxic side effects offers an avenue for relieving cancer patients' pain during the treatment process. Since the advent of nanotechnology, interventions, such as loading appropriate drug combinations into nano-sized carriers and multiple tumor-targeting functional modifications on the carrier surface to enhance the anti-tumor effect and reduce toxic and side effects, have been widely used for treating tumors. RESULTS: Nanocarriers containing doxorubicin hydrochloride (DOX) and salvianolic acid A (Sal A) are spherical with a diameter of about 18 nm; the encapsulation efficiency of both DOX and salvianolic acid A is greater than 80%. E-[c(RGDfK)2]/folic acid (FA) co-modification enabled nanostructured lipid carriers (NLC) to efficiently target a variety of tumor cells, including 4T1, MDA-MB-231, MCF-7, and A549 cells in vitro. Compared with other preparations (Sal A solution, NLC-Sal A, DOX solution, DOX injection, Sal A/DOX solution, NLC-DOX, NLC-Sal A/DOX, and E-[c(RGDfK)2]/FA-NLC-Sal A/DOX) in this experiment, the prepared E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had the best anti-tumor effect. Compared with the normal saline group, it had the highest tumor volume inhibition rate (90.72%), the highest tumor weight inhibition rate (83.94%), led to the highest proportion of apoptosis among the tumor cells (61.30%) and the lowest fluorescence intensity of proliferation among the tumor cells (0.0083 ± 0.0011). Moreover, E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had a low level of nephrotoxicity, with a low creatinine (Cre) concentration of 52.58 µmoL/L in the blood of mice, and no abnormalities were seen on pathological examination of the isolated kidneys at the end of the study. Sal A can antagonize the nephrotoxic effect of DOX. Free Sal A reduced the Cre concentration of the free DOX group by 61.64%. In NLC groups, Sal A reduced the Cre concentration of the DOX group by 42.47%. The E-[c(RGDfK)2]/FA modification reduced the side effects of the drug on the kidney, and the Cre concentration was reduced by 46.35% compared with the NLC-Sal A/DOX group. These interventions can potentially improve the tolerance of cancer patients to chemotherapy. CONCLUSION: The E-[c(RGDfK)2]/FA co-modified DOX/Sal A multifunctional nano-drug delivery system has a good therapeutic effect on tumors and low nephrotoxicity and is a promising anti-cancer strategy.


Assuntos
Doxorrubicina , Portadores de Fármacos , Animais , Ácidos Cafeicos , Linhagem Celular Tumoral , Creatinina , Doxorrubicina/farmacologia , Portadores de Fármacos/farmacologia , Combinação de Medicamentos , Ácido Fólico , Lactatos , Ligantes , Lipídeos , Camundongos , Camundongos Endogâmicos BALB C , Solução Salina
20.
BMC Urol ; 22(1): 157, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36163007

RESUMO

OBJECTIVE: This work focused on investigating the relation of centromeric protein A (CENPA) gene expression with prognosis of papillary renal cell carcinoma (PRCC). METHODS: We obtained data from PRCC cases in TCGA. Thereafter, CENPA levels between the paired PRCC and matched non-carcinoma samples were analyzed by Wilcoxon rank-sum test, while the relations of clinicopathological characteristics with CENPA level were examined by logistic regression and Wilcoxon rank-sum test. The prognostic value of CENPA was assessed by plotting the receiver operating feature curve (ROC) and calculating the value of area under curve (AUC). In addition, relations between clinicopathological characteristics and PRCC survival were analyzed through Kaplan-Meier (KM) and Cox regression analyses. After dividing the total number of patients into the trial cohort and the validation cohort in a ratio of 7:3, we constructed a nomogram in trial cohort according to multivariate Cox regression results for predicting how CENPA affected patient survival and used the calibration curve to verify its accuracy in both cohorts. We also determined CENPA levels within cancer and matched non-carcinoma samples through immunohistochemistry (IHC). Finally, we utilized functional enrichment for identifying key pathways related to differentially expressed genes (DEGs) between PRCC cases with CENPA up-regulation and down-regulation. RESULTS: CENPA expression enhanced in PRCC tissues compared with healthy counterparts (P < 0.001). CENPA up-regulation was related to pathological TNM stage and clinical stage (P < 0.05). Meanwhile, the ROC curves indicated that CENPA had a remarkable diagnostic capacity for PRCC, and the expression of CENPA can significantly improve the predictive accuracy of pathological TNM stage and clinical stage for PRCC. As revealed by KM curves, PRCC cases with CENPA up-regulation were associated with poor survival compared with those with CENPA down-regulation (Risk ratio, RR = 3.07, 95% CI: 1.58-5.97, P = 0.001). In the meantime, univariate as well as multivariate analysis showed an independent association of CENPA with overall survival (OS, P < 0.05) and the nomogram demonstrated superior predictive ability in both cohorts. IHC analysis indicated that PRCC cases showed an increased CENPA positive rate compared with controls. As revealed by functional annotations, CENPA was enriched into pathways associated with neuroactive ligand receptor interactions, cytokine receptor interactions, extracellular matrix regulators, extracellular matrix glycoproteins and nuclear matrisome. CONCLUSION: CENPA expression increases within PRCC samples, which predicts dismal PRCC survival. CENPA may become a molecular prognostic marker and therapeutic target for PRCC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Glicoproteínas , Humanos , Neoplasias Renais/patologia , Ligantes , Prognóstico , Receptores de Citocinas
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