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1.
Clin. transl. oncol. (Print) ; 25(11): 3152-3164, 11 nov. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-226840

RESUMO

Objective Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. Method Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. Results HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. Conclusion Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC (AU)


Assuntos
Humanos , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Proteína HMGB2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Invasividade Neoplásica/genética , Proteínas Nucleares/metabolismo , /genética , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
2.
Clin. transl. oncol. (Print) ; 25(11): 3241-3251, 11 nov. 2023.
Artigo em Inglês | IBECS | ID: ibc-226847

RESUMO

Purpose Metal Regulatory Transcription Factor 1 (MTF1) can be an essential transcription factor for heavy metal response in cells and can also reduce oxidative and hypoxic stresses in cells. However, the current research on MTF1 in gastric cancer is lacking. Methods Bioinformatics techniques were used to perform expression analysis, prognostic analysis, enrichment analysis, tumor microenvironment correlation analysis, immunotherapy Immune cell Proportion Score (IPS) correlation and drug sensitivity correlation analysis of MTF1 in gastric cancer. And qRT-PCR was used to verify MTF1 expression in gastric cancer cells and tissues. Results MTF1 showed low expression in gastric cancer cells and tissues, and low expression in T3 stage compared with T1 stage. KM prognostic analysis showed that high expression of MTF1 was significantly associated with longer overall survival (OS), FP (first progression) and PPS (post-progression survival) in gastric cancer patients. Cox regression analysis showed that MTF1 was an independent prognostic factor and a protective factor in gastric cancer patients. MTF1 is involved in pathways in cancer, and the high expression of MTF1 is negatively correlated with the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs. Conclusion MTF1 is relatively lowly expressed in gastric cancer. MTF1 is also an independent prognostic factor for gastric cancer patients and is associated with good prognosis. It has the potential to be a diagnostic and prognostic marker for gastric cancer (AU)


Assuntos
Humanos , Fatores de Transcrição/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Regulação da Expressão Gênica , Microambiente Tumoral , Biomarcadores Tumorais , Prognóstico
3.
Nefrología (Madrid) ; 43(5)sep.-oct. 2023. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-224869

RESUMO

Background: Diabetic nephropathy (DN) which refers to the cases with biopsy proven kidney lesions, is one of the main complications of diabetes all around the world; however, the underlying biological changes causing DN remain to be understood. Studying the alterations in gene expression profiles could give a holistic view of the molecular pathogenicity of DN and aid to discover key molecules as potential therapeutic targets. Here, we performed a meta-analysis study that included microarray gene expression profiles coming from glomerular samples of DN patients in order to acquire a list of consensus Differentially Expressed Genes (meta-DEGs) correlated with DN. Methods: After quality control and normalization steps, five gene expression datasets (GES1009, GSE30528, GSE47183, GSE104948, and GSE93804) were entered into the meta-analysis. The meta-analysis was performed by random effect size method and the meta-DEGs were put through network analysis and different pathway enrichment analyses steps. MiRTarBase and TRRUST databases were utilized to predict the meta-DEGs related miRNAs and transcription factors. A co-regulatory network including DEGs, transcription factors and miRNAs was constructed by Cytoscape, and top molecules were identified based on centrality scores in the network.(AU)


Antecedentes: La nefropatía diabética (ND), que se refiere a los casos con lesiones renales comprobadas por biopsia, es una de las principales complicaciones de la diabetes en todo el mundo. Sin embargo, los cambios biológicos subyacentes que causan la ND aún no se han entendido. Aquí realizamos un estudio de metaanálisis que incluyó perfiles de expresión génica de micromatrices provenientes de muestras glomerulares de pacientes con ND para adquirir una lista de genes expresados diferencialmente (meta-DEG) de consenso correlacionados con ND. Métodos: Después de los pasos de control de calidad y normalización, se ingresaron en el metaanálisis cinco conjuntos de datos de expresión génica (GES1009, GSE30528, GSE47183, GSE104948 y GSE93804). El metaanálisis se realizó mediante el método de tamaño de efecto aleatorio y los meta-DEG se sometieron a análisis de red y a diferentes pasos de análisis de enriquecimiento de ruta. Se utilizaron las bases de datos MiRTarBase y TRRUST para predecir los factores de transcripción y los miARN relacionados con los meta-DEG. Cytoscape construyó una red de corregulación que incluye DEG, factores de transcripción y miARN, y las moléculas principales se identificaron en función de las puntuaciones de centralidad en la red. (AU)


Assuntos
Humanos , Nefropatias Diabéticas/genética , Transcriptoma , Fatores de Transcrição , Biologia de Sistemas
4.
Arch. esp. urol. (Ed. impr.) ; 76(6): 425-438, 28 aug. 2023. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-224895

RESUMO

Background: Based on publicly available transcriptome and single-cell sequencing data, the current study aimed to explore the molecular mechanisms underlying the involvement of hepatocellular carcinoma-derived growth factor-like 3 (HDGFL3) in prostate cancer (PCA) growth and metastasis. Methods: The Gene Expression Omnibus database was used to download the single cell transcriptome of PCA (GSE193337). Single-cell RNA sequencing (scRNA-seq) data were examined to identify which genes are essential for endothelial cell function. The Cancer Genome Atlas Prostate Adenocarcinoma database provided the RNA sequencing data, and univariate COX regression analysis was introduced to identify the genes that were associated with the prognosis of patients with PCA. Human PCA cell lines PC-3 and DU145 were used in in vitro cellular studies to test the effect of silencing HDGFL3. The results were validated using Transwell® assay, scratch assay, and cell counting kit-8 assay. To support the role of HDGFL3 in PCA, an in vivo animal model of PCA transplantation tumor in nude mice was established. Quantitative reverse transcription polymerase chain reaction was introduced to measure HDGFL3 messenger ribonucleic acid (mRNA) expression levels in tumor tissues from nude mice, and Hematoxylin and Eosin staining was used to identify lung metastasis. Immunohistochemical staining was employed to identify the expression levels of HDGFL3 and hematopoietic progenitor cell antigen CD34+. Results: It was discovered through analysis of the scRNA-seq dataset that HDGFL3, a gene specific to endothelial cells, is linked to a poor prognosis in men with PCA. In addition, HDGFL3 and the expression of genes linked to angiogenesis have a substantial association (AU)


Assuntos
Humanos , Masculino , Regulação Neoplásica da Expressão Gênica , RNA/genética , Sequenciamento do Exoma , Neoplasias da Próstata/genética , Metástase Neoplásica/genética , Fatores de Transcrição
5.
Clin. transl. oncol. (Print) ; 25(7): 1940-1948, jul. 2023. ilus
Artigo em Inglês | IBECS | ID: ibc-222369

RESUMO

The circadian rhythm disorder and abnormal expression of rhythm genes are related to many diseases, especially cancer. Rhythm gene NFIL3 is involved in energy metabolism and immune cell differentiation, and its aberrant expression is associated with metabolic diseases and inflammation. Previously, numerous studies have shown that aberrant NFIL3 expression is associated with tumorigenesis, progression, and chemotherapy resistance. For instance, NFIL3 performs as a nuclear transcription factor, impacts cell proliferation, represses apoptosis, and promotes cancer cell invasion and metastasis by regulating the transcription of target genes. In addition, NFIL3 expressed in cancer cells influences the type and proportion of infiltrated immune cells in the tumor microenvironment. Increased expression of NFIL3 induces the chemotherapy and immunotherapy resistance in cancer. In this review, we summarized the pathological functions of NFIL3 in tumorigenesis, cancer development, and treatment. The rhythm gene NFIL3 can be used as a promising target in cancer therapy in the future (AU)


Assuntos
Humanos , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias/genética , Microambiente Tumoral , Carcinogênese , Ritmo Circadiano/genética , Fatores de Transcrição/metabolismo
6.
Clin. transl. oncol. (Print) ; 25(7): 2116-2126, jul. 2023. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-222382

RESUMO

Objective The Zinc fingers and homeoboxes (ZHX) protein family has been reported to be involved in tumor development; however, it remains controversial whether these proteins can act as promoters or inhibitors of cancer development. The current study focused on the biological role of ZHX2 in ovarian cancer. Methods Tissue microarrays were established using 154 ovarian cancer samples. Immunohistochemical analysis was employed to determine the expression levels of ZHX2 in ovarian cancer samples. The prognostic analysis was performed using the Kaplan–Meier method and compared with a log-rank test. The specific role of ZHX2 in ovarian cancer was investigated in cell lines in vitro. Results It was found that ZHX2 was not significantly overexpressed in ovarian cancer samples; however, its expression was significantly correlated with advanced tumor grade. Patient survival analysis indicated that patients with high expression of ZHX2 exhibited worse overall survival rate compared with those with low expression of ZHX2. Furthermore, univariate and multivariate analyses demonstrated that ZHX2 was an independent prognostic factor of progression-free survival in patients with ovarian cancer. In vitro experiments indicated that inhibition of ZHX2 could significantly suppress ovarian cancer cell proliferation via induction of the apoptotic pathway. Conclusions The data indicated that ZHX2 may be considered a promising biomarker in ovarian cancer and that inhibition of its expression may be a potential therapeutic target in ovarian cancer treatment (AU)


Assuntos
Humanos , Feminino , Proteínas de Homeodomínio/genética , Neoplasias Ovarianas/tratamento farmacológico , Fatores de Transcrição/genética , Dedos de Zinco/genética , Genes Homeobox , Proliferação de Células , Apoptose
7.
Clin. transl. oncol. (Print) ; 25(7): 2265-2276, jul. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-222393

RESUMO

Background Colorectal cancer (CRC) is the major subtype of gastrointestinal malignancy and involves cancer-related genes and signaling pathways to regulate ferroptosis. The present study was conducted to analyze the role of alkB homolog 5 (ALKBH5) in the ferroptosis of CRC cells and provide novel targets for CRC treatment. Methods The transcriptional and protein levels of ALKBH5 and solute carrier family 7 members 11 (SLC7A11) in tissues and cells were determined by qRT-PCR and Western blot assay. HCT116 and SW620 cells were transfected with ALKBH5 overexpression vectors to determine cell viability and levels of reactive oxygen species (ROS), Fe+, glutathione, and glutathione peroxidase 4 using cell counting kit-8, colony formation, fluorescence probe, assay kits, and Western blot assay. The N6-methyladenosine (m6A) level and the enrichment of m6A on SLC7A11 mRNA were measured by m6A quantitative analysis and m6A methylated RNA immunoprecipitation-qPCR, and the mRNA stability was determined after actinomycin D treatment. CRC cells were treated with the combination of SLC7A11 and ALKBH5 overexpression vectors to confirm the mechanism. Nude mice were subcutaneously injected with CRC cells overexpressing ALKBH5. Results ALKBH5 was downregulated in CRC and ALKBH5 overexpression promoted ROS release and ferroptosis. ALKBH5 erased the m6A modification on SLC7A11 mRNA to reduce the mRNA stability of SLC7A11, further reducing SLC7A11 expression. SLC7A11 overexpression reversed the promotive role of ALKBH5 overexpression in ferroptosis. ALKBH5 upregulation mitigated tumor growth in vivo. Conclusions ALKBH5 reduced SLC7A11 transcription by erasing m6A modification, thus promoting the ferroptosis of CRC cells (AU)


Assuntos
Animais , Camundongos , Neoplasias Colorretais/genética , Proteínas Carreadoras de Solutos/genética , Fatores de Transcrição , Espécies Reativas de Oxigênio , Morte Celular , Camundongos Nus , Carcinogênese
8.
J. physiol. biochem ; 79(1): 107-115, feb. 2023. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-215717

RESUMO

Prolonged dexamethasone (DEX) administration causes skeletal muscle atrophy through induction of both oxidative stress and mitochondrial dysfunction. Lipoxin A4 (LXA4) is a recognized antioxidant but its effect against DEX-induced muscle atrophy has not been studied yet. This study aimed to assess the potential ameliorating effect of LXA4 on DEX-induced muscle atrophy and investigate the possible involvement of the mitochondrial dynamics pathway and the redox state in this effect. Forty male rats were divided into four groups; normal control, LXA4-treated, DEX-treated, and LXA4 plus DEX-treated. At the end of the experiment, LXA4 counteracted the effect of DEX on different parameters including muscle weight, muscle strength, serum creatine kinase activity, malondialdehyde and protein carbonyl contents, Na/K-ATPase and citrate synthase activities, mitochondrial transmembrane potential, mitochondrial transcription factor (TFAM), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2). These findings signify the promising therapeutic effect of LXA4 against DEX-induced skeletal muscle atrophy and indicate the possible involvement of LXA4-induced mitochondrial activation in addition to its well-known antioxidant effects. (AU)


Assuntos
Animais , Ratos , Atrofia Muscular , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/farmacologia , Dexametasona , Músculo Esquelético/metabolismo , Fatores de Transcrição/metabolismo
9.
Clin. transl. oncol. (Print) ; 25(1): 243-255, ene. 2023.
Artigo em Inglês | IBECS | ID: ibc-215838

RESUMO

Purpose Prostate cancer (PC) is a heterogeneous malignancy that greatly threatens man’s health. E3 ubiquitin-protein ligase neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) imparts an regulatory role in various malignancies. This study focused on the modulatory mechanism of NEDD4L in proliferation of prostate cancer cells (PCCs) via regulating histone demethylase plant homeodomain finger protein 8 (PHF8/KDM7B) through the ubiquitin–proteasome system. Methods The expression levels of NEDD4L, PHF8, H3 lysine 9 dimethylation (H3K9me2) and activating transcription factor 2 (ATF2) in PC tissues and cell lines were detected via real-time quantitative polymerase chain reaction and Western blotting. After transfection of pcDNA3.1-NEDD4L, pcDNA3.1-PHF8, and pcDNA3.1-ATF2 into PCCs, cell proliferation was assessed via the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Interaction between NEDD4L and PHF8 was identified via the protein immunoprecipitation. The ubiquitination level of PHF8 was determined via the ubiquitination detection. The enrichments of H3K9me2 and PHF8 in the ATF2 promotor region were detected via the chromatin-immunoprecipitation assay. Results PHF8 and ATF2 were highly expressed while NEDD4L was poorly expressed in PC tissues and cells. NEDD4L overexpression reduced proliferation of PCCs. NEDD4L induced degradation of PHF8 via ubiquitination. PHF8 limited the enrichment of H3K9me2 in the ATF2 promotor region and enhanced ATF2 transcription. Up regulation of PHF8 or ATF2 abolished the inhibitory role of NEDD4L in proliferation of PCCs. Conclusion NEDD4L facilitated degradation of PHF8 to limit ATF2 transcription, thereby suppressing proliferation of PCCs. (AU)


Assuntos
Humanos , Masculino , Neoplasias da Próstata/patologia , Fatores de Transcrição/metabolismo , Proliferação de Células , Histona Desmetilases , Proteínas de Homeodomínio , Complexo de Endopeptidases do Proteassoma , Ubiquitinas
10.
Int. microbiol ; 25(4): 789-802, Nov. 2022. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-216246

RESUMO

Eukaryotic cells respond to environmental cues through mitogen activated protein kinase (MAPK) signaling pathways. Each MAPK cascade is specific to particular stimuli and mediates specialized responses through activation of transcription factors. In the budding yeast, Saccharomyces cerevisiae, the pheromone-induced mating pathway and the starvation-responsive invasive growth/filamentation pathway generate their distinct outputs through the transcription factors Ste12 and Tec1, respectively. In this study, we report the functional characterization of these transcription factors in the closely related human opportunistic pathogenic yeast Candida glabrata. Two homologues each for S. cerevisiae TEC1 and STE12 were identified in C. glabrata. Both C. glabrata Tec1 proteins contain the N-terminal TEA DNA-binding domain characteristic of the TEA/ATTS transcription factor family. Similarly, the DNA-binding homeodomain shared by members of the highly conserved fungal Ste12 transcription factor family is present in N-terminus of both C. glabrata Ste12 transcription factors. We show that both C. glabrata STE12 genes are at least partial functional orthologues of S. cerevisiae STE12 as they can rescue the mating defect of haploid S. cerevisiae ste12 null mutant. Knockout of one of the STE12 genes (ORF CAGL0H02145g) leads to decreased biofilm development; a stronger biofilm-impaired phenotype results from loss of both CgSTE12 genes in the double deletion mutant (Cgste12ΔΔ). The transcript levels of one of the TEC1 genes (ORF CAGL0M01716g) were found to be upregulated upon exposure to low pH; its deletion causes slightly increased sensitivity to higher concentrations of acetic acid. Heat shock leads to increase in mRNA levels of one of the STE12 genes (ORF CAGL0M01254g).(AU)


Assuntos
Humanos , Células Eucarióticas , Quinases de Proteína Quinase Ativadas por Mitógeno , Biofilmes , Saccharomyces cerevisiae , Fatores de Transcrição , Candida glabrata , Doenças Transmissíveis , Microbiologia
11.
Clin. transl. oncol. (Print) ; 24(11): 2064-2073, noviembre 2022.
Artigo em Inglês | IBECS | ID: ibc-210135

RESUMO

Prostate cancer (PCa) is the second leading cause of cancer deaths in men. Unfortunately, a very limited number of drugs are available for the relapsed and advanced stages of PCa, adding only a few months to survival; therefore, it is vital to develop new drugs. 5´ AMP-activated protein kinase (AMPK) is a master regulator of cell metabolism. It plays a significant role in the metabolism of PCa; hence, it can serve well as a treatment option for the advanced stages of PCa. However, whether this pathway contributes to cancer cell survival or death remains unknown. The present study reviews the possible pathways by which AMPK plays role in the advanced stages of PCa, drug resistance, and metastasis: (1) AMPK has a contradictory role in promoting glycolysis and the Warburg effect which are correlated with cancer stem cells (CSCs) survival and advanced PCa. It exerts its effect by interacting with hypoxia-induced factor 1 (HIF1) α, pyruvate kinase 2 (PKM2), glucose transporter (GLUT) 1 and pyruvate dehydrogenase complex (PDHC), which are key regulators of glycolysis; however, whether it promotes or discourage glycolysis is not conclusive. It can also exert an anti-CSC effect by negative regulation of NANOG and epithelial–mesenchymal transition (EMT) transcription factors, which are the major drivers of CSC maintenance; (2) the regulatory effect of AMPK on autophagy is also noticeable. Androgen receptors’ expression increases AMPK activation through Calcium/calmodulin-dependent protein kinase 2 (CaMKK2) and induces autophagy. (AU)


Assuntos
Humanos , Proteínas Quinases Ativadas por AMP , Autofagia , Cálcio/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Complexo Piruvato Desidrogenase/metabolismo , Complexo Piruvato Desidrogenase/farmacologia , Piruvato Quinase/metabolismo , Piruvato Quinase/farmacologia , Piruvato Quinase/uso terapêutico , Transdução de Sinais , Fatores de Transcrição/metabolismo
13.
Arch. Soc. Esp. Oftalmol ; 97(9): 504-509, sept. 2022. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-209104

RESUMO

Antecedentes y objetivos OVOL1 es un gen que regula negativamente la transformación mesenquimática, la cual permite a las células epiteliales invadir el estroma. Por otro lado, regula negativamente la c-Myc, que tiene un efecto positivo sobre la proliferación celular. El objetivo de este estudio es evaluar la expresión de OVOL1 y c-Myc en neoplasias escamosas de la superficie ocular (NESO). Pacientes y métodos Estudio de cohorte transversal de 36 muestras que incluían 6 papilomas escamosos, 19 neoplasias intraepiteliales conjuntivales, 6 carcinomas escamosos y 7 conjuntivas normales, que fueron evaluadas mediante técnica inmunohistoquímica contra OVOL1 y c-Myc. La expresión de ambos marcadores fue analizada usando el H-score (intensidad 1-3 multiplicado por el porcentaje de células positivas) Resultados Un 98 y un 100% de las NESO y un 57 y un 71% de las conjuntivas normales expresaron OVOL1 y c-Myc, respectivamente; sin embargo, el promedio del H-score de OVOL1 y c-Myc fue mayor en las NESO que en las conjuntivas normales (p=0,0001 en ambos). Dentro de las NESO, OVOL1 demostró un H-score mayor en las neoplasias intraepiteliales conjuntivales y los papilomas, en comparación con el carcinoma escamoso (p<0,01). c-Myc no mostró diferencias entre los grupos de NESO. Un H-score menor de 35 diferencia un carcinoma escamoso de los otros grupos de NESO con una sensibilidad del 83,3% y una especificidad del 100%. Conclusiones La expresión de OVOL1 es útil para diferenciar un carcinoma escamoso de una neoplasia intraepitelial conjuntival y un papiloma. OVOL1 podría jugar un rol en la capacidad de invasión de las neoplasias escamosas y lo ubica como un potencial blanco terapéutico (AU)


Background and objectives OVOL1 is a gene that negatively regulates mesenchymal transformation, which allows epithelial cells to invade the stroma. On the other hand, it negatively regulates c-Myc, which has a positive effect on cell proliferation. The aim of this study is to evaluate the expression of OVOL1 and c-Myc in ocular surface squamous neoplasia (OSSN). Patients and methods Cross-sectional cohort study of 36 samples including 6 squamous papillomas, 19 conjunctival intraepithelial neoplasms, 6 squamous carcinomas and 7 normal conjunctivae were evaluated using immunohistochemistry against OVOL1 and c-Myc. The expression of both markers was analysed using the H-score (intensity 1-3 multiplied by the percentage of positive cells). Results Percentages of 98 and 100 of the OSSN, and 57 and 71% of the normal conjunctivae expressed OVOL1 and c-Myc respectively, however, the mean H-score of OVOL1 and c-Myc was higher in the OSSN than in normal conjunctivae group (P=.0001 in both). Within the OSSN, OVOL1 demonstrated a higher H-score in the conjunctival intraepithelial neoplasms and papilloma, compared to the squamous carcinoma (P<.01) group. c-Myc did not show differences between the OSSN groups. An H-score lower than 35 differentiates a squamous cell carcinoma from other OSSN lesions with a sensitivity of 83.3% and a specificity of 100%. Conclusions The expression of OVOL1 is a useful tool to differentiate between a squamous carcinoma of conjunctival intraepithelial neoplasms and papilloma. OVOL1 could play a role in the invasiveness of squamous neoplasms and places it as a potential therapeutic target (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias da Túnica Conjuntiva/patologia , Papiloma/patologia , Estudos Transversais , Estudos de Coortes , Proteínas de Ligação a DNA , Fatores de Transcrição , Imuno-Histoquímica
14.
Allergol. immunopatol ; 50(4): 1-9, jul. 2022. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-208888

RESUMO

Monoallelic loss-of-function (LOF) mutations in the phosphatidylinositol 3-kinase (PIK3R1) gene affecting the inter-Src homology 2 domain of the p85α regulatory subunit of phosphoinositide-3-kinase δ (PI3Kδ) cause the activated PI3K δ syndrome (APDS2). APDS2 is defined as a primary antibody deficiency, developmental abnormalities within the B and T lymph cell compartments, and immune dysregulation. The genetic defect of APDS2 is shared with that of the SHORT syndrome, characterized by short stature, joint hyperextensibility, ocular depression, Rieger anomaly, and delayed tooth eruption. LOF variants in an intronic splice site (c.1425+1G.C/A/T) in the PI3KR1 gene have been identified in patients affected with both APDS2 and SHORT syndrome. Herein, we report a novel c.1644-1648del (p.Asp548Glufs*6) variant in a pediatric patient with the APDS2-related immunodeficiency, who presents with mild phenotypic fea-tures of the SHORT syndrome, congenital chest wall deformity, and IgE-mediated food allergy. The same variant was also identified in the patient’s hitherto asymptomatic mother, impli-cating an incomplete penetrance. Regular monitoring by a multidisciplinary team under the pediatric clinical immunologist’s supervision to implement appropriate diagnostic procedures and treatment modalities is of paramount importance. Further studies are required to better define the genotype-phenotype correlation in patients with the PIK3R1 gene mutations and to better delineate the mutual relationship between APDS2 and the SHORT syndrome (AU)


Assuntos
Humanos , Masculino , Lactente , Lipodistrofia/genética , Fosfatidilinositol 3-Quinases/genética , Transtornos do Crescimento/genética , Doenças Metabólicas/genética , Penetrância , Fatores de Transcrição/genética , Síndrome , Mutação , Fenótipo
15.
Clin. transl. oncol. (Print) ; 24(6): 1059-1072, junio 2022.
Artigo em Inglês | IBECS | ID: ibc-203806

RESUMO

PurposeThe long noncoding RNA LINC00261 was reported to be involved in carcinogenesis and has been validated as a tumor suppressor in pancreatic cancer (PC); however, how LINC00261 is regulated has not been fully examined. Here, we attempted to investigate the upstream and downstream targets of LINC00261 in PC.MethodsLINC00261 expression in PC tissues was examined by the Gene Expression Omnibus (GEO) datasets and the Gene Expression Profiling Interactive Analysis (GEPIA) database. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were performed to detect the expression level of LINC00261 in PC cells. The location of LINC00261 in PC cells was identified by RNA fluorescence in situ hybridization (RNA-FISH). Cell Counting Kit-8 (CCK-8), cell apoptosis assay, transwell invasion and migration assays testified the critical role of LINC00261 in PC. The luciferase reporter assay was applied to confirm the binding of LINC00261 to its upstream transcription factor KLF13. The changes in LINC00261 related target protein levels were analyzed by Western blotting assay.ResultsLINC00261 was significantly lower in PC tissues and was mainly concentrated in the nucleus. Overexpression of LINC00261 inhibited the invasion and migration of PC cells. Mechanistically, transcription factor KLF13 was confirmed to inhibit the epithelial-mesenchymal transition (EMT) process of PC cells by promoting the transcription of LINC00261 and suppressing the expression of metastasis-associated proteins, such as matrix metalloproteinase MMP2 and vimentin, thus inhibiting the metastasis of PC.ConclusionLINC00261 regulates PC cell metastasis through the “KLF13-LINC00261-mTOR-P70S6K1-S6” signaling pathway, which provides a significant set of potential PC therapeutic targets.


Assuntos
Humanos , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Repressoras , Transdução de Sinais
16.
Arch. esp. urol. (Ed. impr.) ; 75(5): 459-466, Jun. 28, 2022. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-209233

RESUMO

Purpose: The progress of prostate cancer entails complex contemporaneous tumor developmental events in diverse stages that they are still yet to be clarified. miRNAs might accompany to balance between regulatory and cytotoxic T cells in tumors. Here, we investigated miRNAs and Regulatory T cell (Treg) marker FOXP3 expressions within prostate cancer spectrum. Methods: Thirty-eight prostate cancer patients enrolled within two groups to the study as having Gleason Score ≤ 7 (Group-1) and ≥ 8 (Group-2) that compared to 19 benign prostate hyperplasia controls. Twelve miRNAs expressions were analyzed by real time PCR from paraffin-embedded prostate tissue samples. Correlations between serum PSA levels, immunohistochemical staining of CD3, CD4, FOXP3 and miRNA expressions were analyzed. Results: In our study, hsa-let7c-3p significantly 1,52 (p=0.018) and 1,84 (p=0.0095) fold down- regulated whereas, miR-141-3p was significantly 2,36 (p=0.0006) and 2,24 (p=0.001) fold upregulated in the prostate cancer patients compared to benign prostate hyperplasia in group 1 and 2, respectively. Only CD4 (p=0.004) and PSA (p<0.001) have statistically significant differences among groups when compared to benign prostate hyperplasia. miR-143-p, miR-221-3p, hsa-let7c-3p and miR-17-3p expressions were significantly correlated with regulatory T cell marker FOXP3 expression. Conclusions: For the first time, we reported significantly altered expression levels of miRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143, miR17) and correlations between Treg marker FOXP3 in the aggressive prostate cancer patients suggesting that prostate cancer progression might be under the regulation of crosstalk between Tregs and miRNAs (AU)


Propósito: El progreso del cáncer de próstata implicaeventos complejos de desarrollo tumoral contemporáneo endiversas etapas que aún no se han aclarado. Aquí, investigamos los MIRNAs y el marcador de células T reguladoras(Treg) FOXP3 expresiones dentro del espectro de cáncer depróstata.Métodos: Treinta y ocho pacientes con cáncer depróstata inscritos dentro de dos grupos para el estudio unapuntuación de Gleason ≤ 7 (Grupo-1) y ≥ 8(Grupo-2)que en comparación con 19 controles benignos de hiperplasia de próstata. Doce expresiones miRNAs fueron analizadas por PCR en tiempo real a partir demuestras detejidoprostático incrustado en parafina. Se analizaronlos nivelesde PSA séricos de correlaciónsetween, la tinción inmunohistoquímica de expresiones CD3, CD4, FOXP3 y miRNA.Resultados: En nuestro estudio, has-let7c-3p significativamente 1,52 (p-0.018) y 1,84 (p-0. 0095) plegarsehacia abajo, mientras que, miR-141-3p fue significativamente 2,36 (p-0.0006) y 2,24 (p-0. 001) plegarse reguladoen los pacientes con cáncer de próstata en comparación conla hiperplasia benigna de próstata en los grupos 1 y 2, respectivamente. Sólo CD4 (p-0.004) y PSA (p<0. 001)tienen diferencias estadísticamente significativas entre losgrupos en comparación con la hiperplasia benigna de próstata. las expresiones miR-143-p, miR-221-3p, has-let7c-3py miR-17-3p se correlacionaron significativamente conlaexpresión FOXP3 del marcador de celda T egulatorio r.Conclusiones: Fo laprimera vez,informamos denivelde expresión significativamente alterado demiRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143,miR17) y correlaciones entre el marcador Treg DE Treg33en los pacientes agresivos de cáncer de próstata sugiriendoque la progresión del cáncer de próstata podría estar bajo laregulación de la cruz entre Tregtalks y miR. (AU)


Assuntos
Humanos , Masculino , Fatores de Transcrição/genética , Fatores de Transcrição Forkhead/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Biomarcadores Tumorais , Marcadores Genéticos , Perfilação da Expressão Gênica , MicroRNAs/metabolismo , Antígeno Prostático Específico , Linfócitos T Reguladores/metabolismo
17.
Clin. transl. oncol. (Print) ; 24(5): 941-949, mayo 2022.
Artigo em Inglês | IBECS | ID: ibc-203796

RESUMO

PurposeCutaneous angiosarcoma (CAS) is a rare but typically aggressive malignant vascular neoplasm of the skin. Tumor microenvironment (TME) of CAS and its associations with baseline clinicopathological features and patient outcomes are very important, especially when considering the recent advances in understanding of the tumor biology.Methods/patientsWe retrospectively reviewed medical records of patients who underwent surgical resection for CAS at a tertiary Hospital. The pretreated specimens were evaluated by immunohistochemistry for programmed cell death protein 1 (PD-1) and its ligand (PD-L1), densities of tumor infiltrative lymphocytes (TILs) (CD3+, CD4+, CD8+, CD45RO+, FoxP3+), as well as c-MYC and Ki-67 expressions. Overall survival (OS) was estimated by Kaplan–Meier method and compared with Log-rank test.ResultsA total of 21 CAS patients were identified. Median age was 67 (ranges: 20–81) years, 14 (66.7%) were male, and over 50% had lesions of scalp. Histopathological examination showed a predominantly spindle cell type (57.1%). All patients underwent surgery, 16 (76.2%) were treated further. PD-L1 was positively stained (> 1%) in tumor cells (42.9%) and TILs (23.8%). PD-1 expression (> 1%) was identified in TILs of 11 (52.4%) cases. PD-1/PD-L1 expressions were significantly associated with the higher densities of CD3+, CD4+, CD8+, CD45RO+, and Foxp3+ TILs, but not with patient characteristics or c-MYC or Ki-67 expression. Median OS was 18.5 months (95% CI 6.0–35.9), although no prognostic significance was observed with respect to any clinicopathological features.ConclusionWe characterized TME and its clinical and prognostic association in CAS. PD-1/PD-L1 expressions were significantly associated with TILs subtypes but not with OS.


Assuntos
Humanos , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Fatores de Transcrição , Hemangiossarcoma/metabolismo , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Microambiente Tumoral , Antígeno Ki-67/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Estudos Retrospectivos
18.
Int. microbiol ; 25(1): 17-26, Ene. 2022. ilus
Artigo em Inglês | IBECS | ID: ibc-216009

RESUMO

The life cycle of Ustilago maydis involves alternation of a haploid saprophytic yeast-like stage and a dikaryotic hyphal virulent form. Under in vitro conditions, basidiocarps are formed. Analysis of the transcriptional network of basidiocarp formation revealed the possible involvement of a Tec transcription factor (Tec1, UMAG_02835) in the process. In some Ascomycota, Tec factors are involved in mycelial formation, pathogenesis, and interaction with other regulatory elements, but their role in Basidiomycota species is almost unknown. Accordingly, we proceeded to determine the role of this gene in U. maydis by its mutation. Tec1 was found to be a crucial factor for normal mating, basidiocarp development, and virulence, all of the functions related to the dikaryotic stage dependent of the b genes, whereas dimorphism and resistance to different stress conditions occurring in the haploid stage were not affected in tec1 mutants. The observation that mutants showed a low residual wild-type phenotype suggests the presence of a secondary mechanism that partially compensates the loss of Tec1.(AU)


Assuntos
Humanos , Ustilago maydis , Virulência , Fatores de Virulência , Fatores de Transcrição , Microbiologia
19.
Clin. transl. oncol. (Print) ; 23(9): 1942-1954, sept. 2021. graf
Artigo em Inglês | IBECS | ID: ibc-222193

RESUMO

Purpose Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC). Methods Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model. Results Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG’s effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression. Conclusion We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC (AU)


Assuntos
Humanos , Animais , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Camundongos , Proliferação de Células/efeitos dos fármacos , Genes Supressores de Tumor , Glutamina/metabolismo , Neoplasias Laríngeas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Fatores de Transcrição/genética , Contagem de Células , Progressão da Doença , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Glutamina/farmacologia , Neoplasias Laríngeas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Fatores de Transcrição/metabolismo
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