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The poorly differentiated thyroid carcinoma (THCA) subtype is associated with an aggressive disease course, a less favorable overall prognosis, and an increased risk of distant organ metastasis. In this study, our objective was to explore the potential utility of the Sprouty-related EVH1 domain-containing protein 3 (SPRED3) as a biomarker for early diagnosis and prognosis in THCA patients. The differentially expressed prognostic-related genes associated with THCA were identified by querying The Cancer Genome Atlas (TCGA) database. The difference in the expression of the SPRED3 gene between thyroid carcinoma (THCA) tissues and normal tissues was analyzed using data from The Cancer Genome Atlas (TCGA) and further validated through immunohistochemistry. Univariate and multivariate Cox regression models were used, along with clinical information from THCA patients, to analyze the prognostic value of the SPRED3 gene in THCA patients. Functional enrichment analysis was subsequently performed to elucidate the molecular mechanisms underlying the regulatory effects of the SPRED3 gene on thyroid carcinoma. Additionally, we calculated the percentage of infiltrating immune cells in THCA patients and evaluated their correlation with SPRED3 gene expression. Compared with those in noncancerous thyroid tissue, the gene and protein expression levels of SPRED3 were found to be elevated in thyroid carcinoma tissues. Furthermore, the expression of SPRED3 in thyroid carcinoma exhibited significant correlations with tumor location, histological grade, pathological stage, and tumor node metastasis classification (TNM) stage. Univariate and multivariate Cox proportional hazards (Cox) regression analyses demonstrated that SPRED3 could serve as an independent prognostic factor for predicting the overall survival of THCA patients. The results of functional enrichment analysis suggested the potential involvement of SPRED3 in the regulation of extracellular matrix organization, epidermal development, signaling receptor activator activity, skin development, receptor ligand activity, glycosaminoglycan binding, neuroactive ligandâreceptor interaction, the IL-17 signaling pathway, and the PI3K-Akt signaling pathway. Additionally, there were significant correlations between the expression level of the SPRED3 gene and the infiltration of various immune cells (eosinophils, central memory T cells, neutrophils, macrophages, and NK cells) within the thyroid tumor microenvironment. SPRED3 can be used as a prognostic biomarker in patients with THCA could potentially be therapeutic target for THCA.
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Relevância Clínica , Neoplasias da Glândula Tireoide , Humanos , Biomarcadores , Ligantes , Fosfatidilinositol 3-Quinases , Prognóstico , Neoplasias da Glândula Tireoide/genética , Microambiente TumoralRESUMO
The distinctions in pathological types and genetic subtypes of lung cancer have a direct impact on the choice of treatment choices and clinical prognosis in clinical practice. This study used pathological histological sections of surgically removed or biopsied tumor tissue from 36 patients. Based on a small sample size, millions of spectral data points were extracted to investigate the feasibility of employing intracellular fluorescent fingerprint information to diagnose the pathological types and mutational status of lung cancer. The intracellular fluorescent fingerprint information revealed the EGFR gene mutation characteristics in lung cancer, and the area under the curve (AUC) value for the optimal model was 0.98. For the classification of lung cancer pathological types, the macro average AUC value for the ensemble-learning model was 0.97. Our research contributes new idea for pathological diagnosis of lung cancer and offers a quick, easy, and accurate auxiliary diagnostic approach.
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Receptores ErbB , Neoplasias Pulmonares , Humanos , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , MutaçãoRESUMO
Regulating electromagnetic parameters and thus improving impedance matching characteristics by multi-component design is regarded as a prospective approach to obtain highly efficient electromagnetic wave absorption materials. Whereas, it is still challenging to fabricate microwave absorbers with strong absorption capacity and durability in harsh conditions. Based on the above considerations, three-dimensional porous multi-functional manganese oxide/nickel/carbon microspheres had been designed and prepared through a combined approach of facile solvothermal reactions and subsequent carbonization processes. The textural characteristic examinations demonstrated that, numerous manganese oxide and Ni nanoparticles of 15-20 nm in diameter were well dispersed in the carbon-based microspheres of approximately 0.8-1 µm in size. Microwave absorption property evaluation indicated that the minimum reflection loss reached up to -53.6 dB at 9.5 GHz, and effective absorption bandwidth of 3.7 GHz was achieved at matching thickness of merely 2.0 mm. The electromagnetic wave attenuation mechanisms analysis displayed that excellent impedance matching and various dissipation pathways, including magnetic loss, interfacial and dipole polarization relaxation synergistically contributed to the high microwave absorption performances of the porous composites. Radar cross-sectional simulation and photothermal measurements verified that the materials were supposed to have promising foregrounds in complicated circumstances.
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Obstruction of the colon caused by a fecalith is not a rare condition, but endoscopic attempts at removal of the fecalith are often unsuccessful because of the size of the fecalith and its extremely hard stone-like consistency. We report a case of bowel obstruction of over two weeks' duration caused by a giant colonic fecalith. Conservative treatments including insertion of a gastric tube and enemas failed to resolve the obstruction. After an initial unsuccessful attempt at fecalith removal by colonoscopy using a snare, we successfully resolved the bowel obstruction over the course of subsequent colonoscopies with endoscopic fenestration of the fecalith and placement of a transrectal gastric tube for directed instillation of the enema fluid, and we were able to avoid surgical intervention in this case.
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Impacção Fecal , Obstrução Intestinal , Humanos , Impacção Fecal/diagnóstico , Impacção Fecal/diagnóstico por imagem , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Colo , Colonoscopia/efeitos adversos , Cateterismo/efeitos adversosRESUMO
Gastric cancer (GC) is one of the most common malignancies, leading to millions of deaths each year. Here, we investigated the molecular mechanisms of GC, with a focus on circXRCC5/miR-655-3p/RREB1/UBA2 axis. circXRCC5 was identified in 62 paired cancer specimens and adjacent normal tissues by genome-wide bioinformatics analysis and verified by qRT-PCR and Sanger sequencing. Knockdown or exogenous expression of circXRCC5 was performed to validate the functional significance of circXRCC5 using both in vitro and in vivo assays, including CCK-8, colony formation, EdU incorporation, transwell system, as well as animal experiments. RNA immunoprecipitation, biotinylated RNA pull-down, ChIP, and dual-luciferase assays were employed to validate the regulatory network of circXRCC5/miR-655-3p/RREB1/UBA2. Frequently elevated circXRCC5 in GC tissues and cell lines was associated with poor prognosis of GC patients. Functionally, circXRCC5 overexpression facilitated GC cell proliferation, migration, and invasion, as well as promoted tumor growth and metastasis in vivo. Mechanistically, circXRCC5 served as a sponge of miR-655-3p to induce upregulation of RREB1. RREB1 was identified as a transcriptional activator of UBA2, thus contributing to GC tumorigenesis. Moreover, RNA binding protein (RBP) HNRNPC was proved to interact with circXRCC5 to promote circXRCC5 biogenesis. Collectively, circXRCC5 facilitates GC progression through the HNRNPC/circXRCC5/miR-655-3p/RREB1/UBA2 axis, which might bring novel therapeutic strategies for GC treatment.
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MicroRNAs , Neoplasias Gástricas , Animais , Neoplasias Gástricas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Retroalimentação , Linhagem Celular TumoralRESUMO
A series of structurally modified curcumol derivatives at C-8 position were designed and synthesized, whose structures were confirmed by 1H NMR,13C NMR, and HRMS analysis. The tested compounds were evaluated for in vitro antitumor activity against colorectal cancer cell lines SW620, HCT116, and CaCo2. Many of the tested candidates exhibited higher inhibition efficiency than curcumol. Among them, compound 3 l shows the best inhibitory effect on the viability of SW620 with IC50 value of 19.90 ± 0.64 µM. The structure-activity relationships of these derivatives were discussed, which showed that the introduction of amino or aryl groups tended to increase the anti-cancer activity. In addition, compound 3 l may inhibit cancer cell proliferation through triggering cell apoptosis.
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A new series of C-14 curcumol derivatives as potent anticancer agents were designed and synthesized by click reaction, whose structures were confirmed by 1H NMR,13C NMR, and HRMS analysis. All the synthesized compounds were evaluated for in vitro antitumor activity against colorectal cancer cell lines SW620 and HCT116. Most of them exhibited higher inhibitory activity than curcumol. Especially, compound 3j shows good inhibitory activity against SW620 with IC50 value of 8.10 ± 0.13 µM. The structure-activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry revealed that compound 3j induced SW620 cells apoptosis by facilitating apoptosis-related proteins expressions. Our findings suggested that fluorine functional group on phenyl ring tended to increase the anticancer activity.
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Antineoplásicos , Sesquiterpenos , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Sesquiterpenos/farmacologia , Relação Estrutura-AtividadeRESUMO
BACKGROUND: The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. METHODS: In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. RESULTS: By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. CONCLUSION: We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.
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Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Neoplasias do Colo/mortalidade , Humanos , Prognóstico , Análise de Sobrevida , Microambiente TumoralRESUMO
O-linked glycosylation (O-glycosylation) and N-linked glycosylation (N-glycosylation) are the two most important forms of protein glycosylation, which is an important post-translational modification. The regulation of protein function involves numerous mechanisms, among which protein glycosylation is one of the most important. Core 1 synthase glycoprotein-N-acetylgalactosamine 3-ß-galactosyltransferase 1 (C1GALT1) serves an important role in the regulation of O-glycosylation and is an essential enzyme for synthesizing the core 1 structure of mucin-type O-glycans. Furthermore, C1GALT1 serves a vital role in a number of biological functions, such as angiogenesis, platelet production and kidney development. Impaired C1GALT1 expression activity has been associated with different types of human diseases, including inflammatory or immune-mediated diseases, and cancer. O-glycosylation exists in normal tissues, as well as in tumor tissues. Previous studies have revealed that changes in the level of glycosyltransferase in different types of cancer may be used as potential therapeutic targets. Currently, numerous studies have reported the dual role of C1GALT1 in tumors (carcinogenesis and cancer suppression). The present review reports the role of C1GALT1 in normal development and human diseases. Since the mechanism and regulation of C1GALT1 and O-glycosylation remain elusive, further studies are required to elucidate their effects on development and disease.
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Cleavage factor I m25 is a newly discovered solid tumor-related gene, however, its precise role in cancer pathogenesis has not yet been characterized. Alternative polyadenylation is an RNA-processing mechanism that generates distinct 3'-termini on messenger RNAs, producing messenger RNA isoforms. Different factors influence the initiation and development of this process. As a key factor in alternative polyadenylation, cleavage factor I m25 plays an important role in messenger RNA maturation and cell signal transduction. Moreover, by regulating the process of alternative polyadenylation, it can inhibit the proliferation, invasion, and metastasis of a variety of tumors. Cleavage factor I m25 also acts as an oncogene in select tumors. The present review focuses on the role of cleavage factor I m25 in solid tumors and treatment. Due to the lack of current knowledge regarding the mechanisms of action and regulation of cleavage factor I m25 and alternative polyadenylation, it is necessary to further examine their role in cancer as well as in other diseases.
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Fator de Especificidade de Clivagem e Poliadenilação/genética , Fator de Especificidade de Clivagem e Poliadenilação/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Animais , Transformação Celular Neoplásica , Gerenciamento Clínico , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/patologia , Neoplasias/terapia , Especificidade de Órgãos/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
The retinoid-interferon-induced mortality-19 (GRIM-19) gene has been identified as a negative regulator associated with tumor development. The current study created a model of an orthotopically implanted hepatocarcinoma tumor to verify the inhibitory effect of GRIM-19 in vivo. After treatment with GRIM-19 carried by attenuated Salmonella, transplanted tumors were measured with an Imaging System. The expression of GRIM-19, Stat3/p-Stat3, cyclinD1, CDK4, PCNA, Bax/Bcl-2, cleaved caspase-9/3, VEGF, and MMP-2/9 was determined using immunohistochemistry and Western blot analysis. The cell cycle was assessed using flow cytometry (FCM). Apoptosis was determined using FCM and a TUNEL assay. Results indicated that GRIM-19 overexpression resulted in inhibition of peritoneal metastasis, induction of cell cycle arrest, and apoptosis in vivo. In addition, the expression of Stat3/p-Stat3 was down-regulated by GRIM-19. These results suggest that GRIM-19 overexpression could suppress the growth of orthotopically implanted hepatocarcinoma tumors by reversing the regulation of the Stat3 signaling pathway. This approach could potentially be a powerful treatment for hepatocarcinoma.
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Vetores Genéticos/administração & dosagem , Neoplasias Hepáticas/terapia , NADH NADPH Oxirredutases/genética , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose/genética , Carcinogênese/genética , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/secundário , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral/transplante , Proliferação de Células/genética , Modelos Animais de Doenças , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Terapia Genética/métodos , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Terapia de Alvo Molecular/métodos , NADH NADPH Oxirredutases/metabolismo , Neoplasias Peritoneais/prevenção & controle , Salmonella typhimurium/genética , Transdução de Sinais/genética , Resultado do TratamentoRESUMO
RATIONALE: Primary malignant melanoma of the esophagus (PMME) is a rare malignancy that only accounts for <2% of all primary esophageal tumors. Here, we report the even rarer occurrence of PMME in combination with poorly differentiated mucinous adenocarcinoma of the stomach. PATIENT CONCERNS: A 64-year-old man was presented to the hospital with >1 month of eating dysphagia. Enhanced computed tomography (CT) scan only found a space-occupying lesion in the lower esophagus with moderate enhancement. However, gastroscope showed not only esophageal masses, but also gastric mucosa changes. DIAGNOSES: Poorly differentiated mucinous adenocarcinoma and PMME were diagnosed based on pathological biopsy and immunohistochemical methods. INTERVENTIONS: The patient underwent laparoscopic gastric cancer radical surgery, esophageal resection, and colonic replacement of the esophagus. OUTCOMES: Abdominal CT and esophagography performed 1 week after surgery showed that it was consistent with postoperative changes without other abnormalities. However, the patient died 3 months after discharge without receiving any other treatment. LESSONS: This case suggests more attention should be drawn to the diagnosis of multiple primary malignant neoplasms in elder patients, and also highlights the need to fulfill comprehensive examinations before surgery in case of misdiagnosis. Besides, it is challenging to finding a reasonable treatment for such rare condition.
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Adenocarcinoma Mucinoso/diagnóstico , Neoplasias Esofágicas/diagnóstico , Melanoma/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Diagnóstico Diferencial , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Evolução Fatal , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
RATIONALE: Primary renal lymphoma (PRL) is a rare malignancy due to the absence of lymphatic tissues in the kidney, and patients with PRL have been reported to have a poor prognosis due to its rapid invasiveness and limited treatment strategies. Colon cancer is the third most common cancer, and has a high mortality rate. Both malignant diseases predominantly affected elderly men; however, a case with concomitant occurrence of the 2 cancers is extremely rare. PATIENT CONCERNS: A 78-year-old male patient with abdominal pain came to our hospital. Computed tomography (CT) indicated malignant masses in the left kidney, left adrenal gland, and the lower part of the descending colon. DIAGNOSES: PRL and colon cancer were diagnosed based on pathological examinations. INTERVENTIONS: The patient was treated with laparoscopic radical nephrectomy and laparoscopic radical resection of colon cancer. OUTCOMES: The patient was then transferred to the intensive care unit (ICU) because of poor condition after surgery. He died 3 months after discharge without receiving any other treatment. LESSONS: It is worth thinking about whether surgery was reasonable for elderly patients with double malignancies, or palliative treatment to improve the quality of life was more meaningful. This case also contributes to the understanding of the 2 malignancies and highlights the need to pay more attention to patients with multiple primary malignant neoplasms (MPMNs), explore genetic features, and investigate treatments with more survival benefits.
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Adenocarcinoma/diagnóstico , Neoplasias do Colo/diagnóstico , Neoplasias Renais/diagnóstico , Linfoma não Hodgkin/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Cuidados Críticos , Diagnóstico Diferencial , Evolução Fatal , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Masculino , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgiaRESUMO
BACKGROUND: This study aimed to identify factors that affect the prognosis of budesonide therapy for Crohn's disease patients. METHOD: Change in Crohn's disease activity index (CDAI) scores at latest follow-up after budesonide therapy reported by individual studies were pooled to gain overall effect size under random effects model and then metaregression analyses were performed to identify factors affecting the change in CDAI scores after budesonide treatment. RESULTS: Fifteen studies (1875 patients; age, 35.6 years [95% confidence interval (CI): 34.1, 37.0]; 41.66% [95% CI: 37.44, 45.88] males; 33.3% [95% CI: 24.3, 42.3] smokers; weight, 64.7 kg [95% CI: 62.71 66.6] and height, 168 cm [95% CI: 165, 171]) were included. Disease duration was 7.0 years [95% CI: 5.7, 8.2] and duration of the current episode was 3.1 months [95% CI: 1.7, 4.4]. Proportion of patients with prior resection was 42% [95% CI: 34%, 50%]. The disease was 21% in the ileum, 61% in ileocecum, and 18% in the colon. Budesonide dose was 8.83 mg/d [95% CI: 7.52, 10.14]. In a follow-up duration of 21.0 weeks [95% CI: 15.2, 26.8], budesonide treatment was associated with improvement in CDAI score of -117.8 [95% CI: -134.0, -102.0]. The magnitude of the change in CDAI score at the latest follow-up was significantly inversely associated with the percentage of smokers, but positively associated with the baseline CDAI score and duration of the current episode. CONCLUSION: Budesonide therapy to Crohn's disease patients appears to be more effective in patients with the more serious condition. Smoking may also affect the prognosis.
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Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Doença de Crohn/tratamento farmacológico , Índice de Gravidade de Doença , Doença de Crohn/etiologia , Doença de Crohn/patologia , Humanos , Prognóstico , Fatores de Risco , Fumar/efeitos adversosRESUMO
Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease (EBV+ T-LPD) is extremely rare. Primary acute or chronic active Epstein-Barr virus infection triggers EBV+ T-LPD's onset and the disease involves clonal proliferation of infected T-cells with activated cytotoxic phenotype. The adult-onset EBV+ T-LPD (ASEBV+ T-LPD) is even rarer and needs to be extensively studied. Further, according to literature review, it is a challenge to find patients who are immunocompetent and diagnosed with ASEBV+ T-LPD involving gastrointestinal tract. This case report discusses a previously healthy middle aged woman who presented with unique symptoms mimicking inflammatory bowel disease, and required a total colectomy and terminal ileum rectomy, as reveled by endoscopic examinations, due to severe gastrointestinal bleeding. Post-surgery histopathological findings were confirmatory for the diagnosis of ASEBV+ T-LPD (II: Borderline). This patient died 7 months after the diagnosis.
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Infecções por Vírus Epstein-Barr/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Intestinos/patologia , Transtornos Linfoproliferativos/diagnóstico , Linfócitos T/imunologia , Proliferação de Células , Doença Crônica , Colectomia , Citotoxicidade Imunológica , Diagnóstico Diferencial , Diarreia , Evolução Fatal , Feminino , Hemorragia , Herpesvirus Humano 4/fisiologia , Humanos , Ativação Linfocitária , Pessoa de Meia-IdadeRESUMO
Small ubiquitinlike modifier proteins are involved in tumorigenesis; however, the potential effects and functions of the family member ubiquitinlike modifieractivating enzyme 2 (UBA2) on colorectal cancer are not clear. The present study aimed to examine the effects of UBA2 on the proliferation of colorectal cancer cells in vitro and in vivo. The mRNA and protein expression levels of UBA2 in patients with colorectal cancer were measured by reverse transcriptionquantitative polymerase chain reaction and immunohistochemistry, respectively. UBA2 expression levels in colorectal cancer tissues were significantly increased compared with the paracancerous normal tissues. The expression of UBA2 was also associated with higher stage colorectal cancer and poor prognosis. MTT and colony formation assays were used to examine proliferation in colorectal cancer cell lines. Flow cytometry was performed to examine the effects of UBA2 on the cell cycle and apoptosis of colorectal cancer cell lines and protein expression levels were examined by western blotting. Athymic nude mice were used to examine the ability of transfected colorectal cancer cells to form tumors in vivo. Downregulation of UBA2 inhibited the proliferation of colorectal cancer cell lines in vitro and in vivo through the regulation of cell cycle associated protein expression and apoptosis. Furthermore, downregulation of UBA2 decreased the expression levels of cyclin B1, Bcell lymphoma-2, phosphorylated protein kinase B and E3 ubiquitinprotein ligase MDM2 in colorectal cancer cells, whereas the expression levels of p21 and p27 were increased. UBA2 was demonstrated to serve an essential role in the proliferation of colorectal cancer and may be used as a potential biomarker to predict prognosis and as a therapeutic target in colorectal cancer.
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Neoplasias Colorretais/genética , Enzimas Ativadoras de Ubiquitina/genética , Adulto , Idoso , Animais , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Enzimas Ativadoras de Ubiquitina/metabolismoRESUMO
AIM: To investigate the function and mechanism of ubiquitin-like modifier activating enzyme 2 (Uba2) in progression of gastric cancer (GC) cells. METHODS: Uba2 level in patients with GC was analyzed by Western blotting and immunohistochemistry. MTT and colony formation assays were performed to examine cell proliferation. Flow cytometry was used for cell cycle analysis. Wound healing and Transwell assays were conducted to examine the effects of Uba2 on migration and invasion. Expression levels of cell cycle-related proteins, epithelial-mesenchymal transition (EMT) biomarkers, and involvement of the Wnt/ß-catenin pathway was assessed by Western blotting. Activation of the Wnt/ß-catenin pathway was confirmed by luciferase assay. RESULTS: Uba2 expression was higher in GC than in normal tissues. Increased Uba2 expression was correlated with tissue differentiation, Lauren's classification, vascular invasion, and TNM stage, as determined by the analysis of 100 GC cases (P < 0.05). Knock-down of Uba2 inhibited GC cell proliferation, induced cell cycle arrest, and altered expression of cyclin D1, P21, P27, and Bcl-2, while up-regulation of Uba2 showed the opposite effects. The wound healing and Transwell assays showed that Uba2 promoted GC cell migration and invasion. Western blotting revealed alterations in EMT biomarkers, suggesting the role of Uba2 in EMT. Furthermore, the luciferase reporter assay indicated the involvement of the Wnt/ß-catenin signaling pathway as a possible modulator of Uba2 oncogenic functions. CONCLUSION: Uba2 plays a vital role in GC cell migration and invasion, possibly by regulating the Wnt/ß-catenin signaling pathway and EMT.
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Movimento Celular , Neoplasias Gástricas/patologia , Enzimas Ativadoras de Ubiquitina/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estômago/patologia , Regulação para CimaRESUMO
Numerous genetic alterations associated with cancer progression have the potential to serve as biomarkers for the early diagnosis of cancer. Numerous studies have suggested that claudin proteins, which are the primary components of tight junction structures, are associated with the regulation of cell polarity and cell differentiation. To investigate the expression profiles of the tight junction proteins claudin2, 5, 7 and 8 in gastric carcinoma, immunohistochemical analysis, western blotting and reverse transcriptionquantitative polymerase chain reaction analysis was used to detect the expression profiles of these claudin proteins in gastric carcinoma tissues and in homologous nonneoplastic mucosal tissues. According to the present study, the expression levels of claudin7 and claudin8 were downregulated, while the expression of claudin5 was upregulated in gastric carcinoma tissues compared with in nonneoplastic mucosal tissues. Additionally, no notable difference was observed between claudin2 expression in gastric carcinoma tissues and nonneoplastic mucosae. Correlations between claudin7 and 8 expression and lymphatic metastasis in gastric carcinoma tissues were additionally reported. In summary, the present study revealed the distinct expression profiles of claudin5, 7 and 8 in nonneoplastic mucosal tissues and gastric carcinoma tissues. Furthermore, the expression of these claudin proteins was highly associated with metastatic progression and prognosis in patients with gastric carcinoma, and had predictive value for the metastasis and survival of patients with gastric carcinoma.
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Claudinas/biossíntese , Mucosa Gástrica/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Claudinas/genética , Feminino , Mucosa Gástrica/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
Colorectal cancer is a serious threat to human health, and has a high mortality rate. There is currently no effective therapy for end-stage colorectal cancer. In recent years, molecular targeted therapy has received increasing attention for cancer treatment. In particular, the role of Uba2, a vital component of SUMO-activating enzyme, has been highlighted, which plays important roles in the progression of certain cancers; however, its role in colorectal cancer remains unclear. Accordingly, the aim of this study was to evaluate the relationship between Uba2 and colorectal cancer. Uba2 expression was knocked down in two colorectal cancer cell lines, and gene microarray analysis was conducted, followed by proliferation, migration, and invasion assays. Uba2 knockdown influenced the expression of several genes, and significantly inhibited the proliferation, migration, and invasion of cancer cells. To determine the underlying mechanism, the expression of related signaling pathways and molecules was evaluated in the knockdown cell lines. Overall, the results suggest that Uba2 participates in the progression, invasion, and metastasis of colorectal cancer, and the possible mechanism is via regulating the Wnt signaling pathway and enhancing epithelial-mesenchymal transition behaviors of colorectal cancer cells. Therefore, Uba2 is expected to be an important oncoprotein and potential therapeutic target in colorectal cancer.
Assuntos
Movimento Celular , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Enzimas Ativadoras de Ubiquitina/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Enzimas Ativadoras de Ubiquitina/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMO
The blood-spinal cord barrier (BSCB) plays a key role in maintaining the microenvironment and is primarily composed of tight junction proteins and nonfenestrated capillary endothelial cells. After injury, BSCB damage results in increasing capillary permeability and release of inflammatory factors. Recent studies have reported that haem oxygenase-1 (HO-1) fragments lacking 23 amino acids at the C-terminus (HO-1C[INCREMENT]23) exert novel anti-inflammatory and antioxidative effects in vitro. However, no study has identified the role of HO-1C[INCREMENT]23 in vivo. We aimed to investigate the protective effects of HO-1C[INCREMENT]23 on the BSCB after spinal cord injury (SCI) in a rat model. Here, adenoviral HO-1C[INCREMENT]23 (Ad-GFP-HO-1C[INCREMENT]23) was intrathecally injected into the 10th thoracic spinal cord segment (T10) 7 days before SCI. In addition, nuclear and cytoplasmic extraction and immunofluorescence staining of HO-1 were used to examine the effect of Ad-GFP-HO-1C[INCREMENT]23 on HO-1 nuclear translocation. Evan's blue staining served as an index of capillary permeability and was detected by fluorescence microscopy at 633 nm. Western blotting was also performed to detect tight junction protein expression. The Basso, Beattie and Bresnahan score was used to evaluate kinematic functional recovery through the 28th day after SCI. In this study, the Ad-GFP-HO-1C[INCREMENT]23 group showed better kinematic functional recovery after SCI than the Ad-GFP and Vehicle groups, as well as smaller reductions in TJ proteins and capillary permeability compared with those in the Ad-GFP and Vehicle groups. These findings indicated that Ad-GFP-HO-1C[INCREMENT]23 might have a potential therapeutic effect that is mediated by its protection of BSCB integrity.