RESUMO
BACKGROUND: Laminin subunit gamma-1 (LAMC1) is a major extracellular matrix molecule involved in the tumor microenvironment. Knowledge of the biological features and clinical relevance of LAMC1 in cancers remains limited. METHODS: We conducted comprehensive bioinformatics analysis of LAMC1 gene expression and clinical relevance in pan-cancer datasets of public databases and validated LAMC1 expression in glioma tissues and cell lines. The association and regulatory mechanism between hypoxia inducible factor-1α (HIF-1α) and LAMC1 expression were explored. RESULTS: LAMC1 expression in most cancers in The Cancer Genome Atlas (TCGA) including glioma was significantly higher than that in normal tissues, which had a poor prognosis and were related to various clinicopathological features. Data from the Chinese Glioma Genome Atlas also showed high expression of LAMC1 in glioma associated with poor prognoses. In clinical glioma tissues, LAMC1 protein was highly expressed and correlated to poor overall survival. LAMC1 knockdown in Hs683 glioma cells attenuated cell proliferation, migration, and invasion, while overexpression of LAMC1 in U251 cells leads to the opposite trend. Most TCGA solid cancers including glioma showed enhancement of HIF-1α expression. High HIF-1α expression leads to adverse prognosis in gliomas, besides, HIF-1α expression was positively related to LAMC1. Mechanistically, HIF-1α directly upregulated LAMC1 promotor activity. Hypoxia (2% O2)-treated Hs683 and U251 cells exhibited upregulated HIF-1α and LAMC1 expression, which was significantly attenuated by HIF-1α inhibitor YC-1 and accompanied by attenuated cell proliferation and invasion. CONCLUSIONS: High expression of LAMC1 in some solid tumors including gliomas suggests a poor prognosis. The hypoxic microenvironment in gliomas activates the HIF-1α/LAMC1 signaling, thereby promoting tumor progression. Targeted intervention on the HIF-1α/LAMC1 signaling attenuates cell growth and invasion, suggesting a new strategy for glioma treatment.
Assuntos
Regulação Neoplásica da Expressão Gênica , Glioma , Subunidade alfa do Fator 1 Induzível por Hipóxia , Laminina , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Prognóstico , Laminina/metabolismo , Laminina/genética , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Masculino , Reprodutibilidade dos Testes , Feminino , Movimento Celular/genética , Invasividade Neoplásica , Bases de Dados Genéticas , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genéticaRESUMO
The dynamic changes of RNA N6-methyladenosine (m6A) during cancer progression participate in various cellular processes. However, less is known about a possible direct connection between upstream regulator and m6A modification, and therefore affects oncogenic progression. Here, we have identified that a key enzyme in N4-acetylcytidine (ac4C) acetylation NAT10 is highly expressed in human osteosarcoma tissues, and its knockdown enhanced m6A contents and significantly suppressed osteosarcoma cell growth, migration and invasion. Further results revealed that NAT10 silence inhibits mRNA stability and translation of m6A reader protein YTHDC1, and displayed an increase in glucose uptake, a decrease in lactate production and pyruvate content. YTHDC1 recognizes differential m6A sites on key enzymes of glycolysis phosphofructokinase (PFKM) and lactate dehydrogenase A (LDHA) mRNAs, which suppress glycolysis pathway by increasing mRNA stability of them in an m6A methylation-dependent manner. YTHDC1 partially abrogated the inhibitory effect caused by NAT10 knockdown in tumor models in vivo, lentiviral overexpression of YTHDC1 partially restored the reduced stability of YTHDC1 caused by lentiviral depleting NAT10 at the cellular level. Altogether, we found ac4C driven RNA m6A modification can positively regulate the glycolysis of cancer cells and reveals a previously unrecognized signaling axis of NAT10/ac4C-YTHDC1/m6A-LDHA/PFKM in osteosarcoma. Video Abstract.
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Citidina/análogos & derivados , Osteossarcoma , Fosfofrutoquinases , Humanos , Lactato Desidrogenase 5/metabolismo , Fosfofrutoquinases/metabolismo , Acetilação , RNA/metabolismo , Glicólise/genética , Osteossarcoma/patologia , Fosfofrutoquinase-1 Muscular/metabolismo , Fatores de Processamento de RNA/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Acetiltransferases N-Terminal/metabolismoRESUMO
BACKGROUND: Stonin1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the immune role of STON1 in kidney renal clear cell carcinoma (KIRC). METHODS: We undertook bioinformatics analyses of the expression and clinical significance of STON1 in KIRC through a series of public databases, and the role of STON1 in the tumor microenvironment and the predictive value for immunotherapy and targeted treatment in KIRC were identified with R packages. STON1 expression was validated in clinical KIRC tissues as well as in KIRC and normal renal tubular epithelial cells. RESULTS: Through public databases, STON1 mRNA was found to be significantly downregulated in KIRC compared with normal controls, and decreased STON1 was related to grade, TNM stage, distant metastasis and status of KIRC patients. Compared with normal controls, STON1 was found to be downregulated in KIRC tissues and cell lines. Furthermore, OncoLnc, Kaplan-Meier, and GEPIA2 analyses also suggested that KIRC patients with high STON1 expression had better overall survival. The high STON1 group with enriched immune cells had a more favorable prognosis than the low STON1 group with decreased immune cells. Single sample Gene Set Enrichment Analysis and Gene Set Variation Analysis indicated that STON1 creates an immune non-inflamed phenotype in KIRC. Moreover, STON1 was positively associated with mismatch repair proteins and negatively correlated with tumor mutational burden. Furthermore, Single sample Gene Set Enrichment Analysis algorithm and Pearson analysis found that the low STON1 group was more sensitive to immune checkpoint blockage whereas the high STON1 group was relatively suitable for targeted treatment. CONCLUSIONS: Decreased STON1 expression in KIRC leads to clinical progression and poor survival. Mechanically, low STON1 expression is associated with an aberrant tumor immune microenvironment. Low STON1 is likely to be a favorable indicator for immunotherapy response but adverse indicator for targeted therapeutics in KIRC.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Microambiente Tumoral/genética , Carcinoma de Células Renais/genética , Imunoterapia , Neoplasias Renais/genética , Rim , PrognósticoRESUMO
BACKGROUND: This study explored the feasibility of using EEG gamma-band (30-49 Hz) power as an index of cue-elicited craving in METH-dependent individuals. METHODS: Twenty-nine participants dependent on methamphetamine (METH) and 30 healthy participants were instructed to experience a METH-related virtual reality (VR) social environment. RESULTS: Individuals with METH dependence showed significantly stronger self-reported craving and higher gamma power in a VR environment than healthy individuals. In the METH group, the VR environment elicited a significant increase in gamma power compared with the resting state. The METH group then received a VR counterconditioning procedure (VRCP), which was deemed useful in suppressing cue-induced reactivity. After VRCP, participants showed significantly lower self-reported craving scores and gamma power when exposed to drug-related cues than the first time. CONCLUSIONS: These findings suggest that the EEG gamma-band power may be a marker of cue-induced reactivity in patients with METH dependence.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Humanos , Fissura , Sinais (Psicologia) , EletroencefalografiaRESUMO
BACKGROUND: Epithelial-mesenchymal transition (EMT) may be one of the reasons for the failure in some clinical trials regarding histone deacetylase inhibitors (HDACIs)-treated solid tumors. We investigated the effects of a pan-HDACI trichostatin A (TSA) on the proliferation and EMT of nasopharyngeal carcinoma (NPC) cells. METHODS: Poorly-differentiated NPC cell line CNE2 and undifferentiated C666-1 were treated with various concentrations of TSA, the cell viability was assessed by CCK-8 assay, the morphology was photographed, and the mRNA level of HDACs was assessed by semiquantitative PCR. After determination the cell cycle distributions, cells were subjected to western blotting analysis of cell cycle and EMT-associated genes expression. And the changes in migration ability were assessed by transwell migration assay and scratch wound healing assay. Finally, histone deacetylases activator ITSA-1 was used to assess the reverse of TSA-induced changes in NPC cells. RESULTS: TSA inhibited the proliferation of CNE2 and C666-1 cells in a concentration-dependent manner and arrested the cell cycle at G1 phases. TSA reduced PCNA, cyclin D1, cyclin E1, CDK2, p16 and p21 expressions and stimulated CDK6 levels. TSA stimulation for 48 h could effectively induce the EMT in CNE2 and C666-1 cells, which showed an increase of spindle-like cells and promoted expression of Vimentin and Snail1 expression in a concentration-dependent manner. Surprisingly, this short period of TSA treatment that induced EMT also impeded the migration ability of CNE2 and C666-1 cells. Interestingly, ITSA-1 rescued TSA-impeded CNE2 and C666-1 cells' proliferation, migration and HDACs expression, also re-induced the cells to turn into epithelial cell phenotypes. CONCLUSIONS: These results indicate that short-term stimulation of TSA effectively inhibits cell proliferation and induce EMT-like changes in NPC cells but not increase its invasion ability.
Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Ácidos Hidroxâmicos/uso terapêutico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Fatores de TempoRESUMO
BACKGROUND: Attention ability can be subdivided into three functionally independent networks, i.e., alerting network, orienting network, and executive network. Previous literature has documented that deficits in attention are a common consequence of HIV infection. However, the precise nature of deficits of attention in HIV-infected patients is poorly understood. Accordingly, the aim of the study was to identify whether the HIV-infected patients showed a specific attention network deficit or a general attentional impairment. METHODS: We investigated 27 HIV-infected patients and 31 normal controls with the Attention Network Test (ANT). RESULTS: The patients exhibited less efficient alerting network and executive network than controls. No significant difference was found in orienting network effect between groups. Our results also indicate a tendency for poorer efficiency on alerting attention and executive attention in patients with CD4 ≤ 200. CONCLUSIONS: Our findings suggest that HIV-infected patients exhibited selective impairments of attention network of alerting and executive control. The link between lower CD4 T cell count and poorer attention network function imply the importance of starting antiretroviral therapy earlier to avoid irreversible neurocognitive impairment.
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Atenção/fisiologia , Função Executiva/fisiologia , Infecções por HIV/complicações , Adolescente , Adulto , Contagem de Linfócito CD4 , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Transtornos Neurocognitivos/virologia , Testes Neuropsicológicos , Orientação/fisiologia , Tempo de Reação/fisiologiaRESUMO
The representational momentum for physical state changes refers to the fact that we remember objects as more changed in physical state than they actually were. It has been well documented that depressive disorder is associated with impairment of time perception. Thus, the present work was conducted with the aim to investigate the representational momentum for physical state changes in patients with depressive disorder, firstly. Forty patients with depressive disorder and forty-two healthy controls were administrated with the task of representational momentum for physical state changes and task of time perception. The stimulus comprises 10 videos showing object state changes (e.g., ice melting). During playing, the video would stop and immediately be obscured by mosaics at a specific point. Participants select from three detection images (the exact frame of the video just be masked, the frame after that, and the frame before that) to test representational momentum and estimate the duration of the video in seconds to test time perception. The depressive group showed diminished representational momentum (i.e., lower scores on the task of representational momentum) than normal controls (U = 215.00, Z = -5.83, p < 0.001). In addition, the scores on the task of representational momentum were significantly positively related with the scores on the task of time perception among depressive group (r = 0.446, p = 0.004). The findings indicate that patients with depressive disorder may exhibit diminished representational momentum for physical states, which may be correlated with their impairment of time perception.
Assuntos
Percepção do Tempo , Humanos , Masculino , Feminino , Adulto , Percepção do Tempo/fisiologia , Transtorno Depressivo/fisiopatologia , Adulto Jovem , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estimulação LuminosaRESUMO
OBJECTIVE: Dendrobin A, a typical active ingredient of the traditional Chinese medicine Dendrobium nobile, has potential clinical application in cancer treatment; however, its effect and mechanism in anti-hepatocellular carcinoma (HCC) remain unsolved. METHOD: The effects of Dendrobin A on the viability, migration, invasion, cycle, apoptosis, and epithelial-mesenchymal transition of HepG2 and SK-HEP-1 cells were verified by in vitro experiments. mRNA sequencing was performed to screen the differentially expressed genes (DEGs) of HCC cells before and after Dendrobin A treatment, following GO enrichment and KEGG signaling pathway analyses. Mechanistically, molecular docking was used to evaluate the binding of Dendrobin A with proteins p65 and p50, before further verifying the activation of nuclear factor kappa-B (NF-κB) signaling. Finally, the antiproliferative effect of Dendrobin A on HCC cells was explored through animal experiments. RESULTS: Dendrobin A arrested cell cycle, induced apoptosis, and inhibited proliferation, migration, invasion, and blocked epithelial-mesenchymal transition in HepG2 and SK-HEP-1 cells. mRNA sequencing identified 830 DEGs, involving various biological processes. KEGG analysis highlighted NF-κB signaling. Molecular docking revealed strong binding of Dendrobin A with p65 and p50 proteins, and western blotting confirmed reduced levels of p-p65 and p-p50 in HCC cells post Dendrobin A treatment. NF-κB agonist PMA reversed Dendrobin A-inhibited cell proliferation migration and invasion. In vivo experiments showed that Dendrobin A inhibited HCC cell growth. CONCLUSION: Our findings suggest that Dendrobin A exhibits anti-HCC properties by inhibiting the activation of the NF-κB pathway. These results provide a scientific basis for utilizing Dendrobium nobile in anti-HCC therapies.
Assuntos
Apoptose , Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Dendrobium , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , Simulação de Acoplamento Molecular , NF-kappa B , Transdução de Sinais , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , NF-kappa B/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Dendrobium/química , Células Hep G2 , Animais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Camundongos Nus , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MasculinoRESUMO
Hyperinflammatory responses are pivotal in the cardiomyocyte senescence pathophysiology, with IL33 serving as a crucial pro-inflammatory mediator. Our previous findings highlighted RND3's suppressive effect on IL33 expression. This study aims to explore the role of RND3 in IL33/ST2 signaling activation and in cardiomyocyte senescence. Intramyocardial injection of exogenous IL33 reduces the ejection fraction and fractional shortening of rats, inducing the appearance of senescence-associated secretory phenotype (SASP) in myocardial tissues. Recombinant IL33 treatment of AC16 cardiomyocytes significantly upregulated expression of SASP factors like IL1α, IL6, and MCP1, and increased the p-p65/p65 ratio and proportions of SA-ß-gal and γH2AX-positive cells. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) and ST2 antibody astegolimab treatments mitigated above effects. RND3 gene knockout H9C2 cardiomyocytes using CRISPR/Cas9 technology upregulated IL33, ST2L, IL1α, IL6, and MCP1 levels, decreased sST2 levels, and increased SA-ß-gal and γH2AX-positive cells. A highly possibility of binding between RND3 and IL33 proteins was showed by molecular docking and co-immunoprecipitation, and loss of RND3 attenuated ubiquitination mediated degradation of IL33; what's more, a panel of ubiquitination regulatory genes closely related to RND3 were screened using qPCR array. In contrast, RND3 overexpression in rats by injection of AAV9-CMV-RND3 particles inhibited IL33, ST2L, IL1α, IL6, and MCP1 expression in cardiac tissues, decreased serum IL33 levels, and increased sST2 levels. These results suggest that RND3 expression in cardiomyocytes modulates cell senescence by inhibiting the IL33/ST2/NF-κB signaling pathway, underscoring its potential as a therapeutic target in cardiovascular senescence.
Assuntos
Senescência Celular , Interleucina-33 , Miócitos Cardíacos , Transdução de Sinais , Animais , Masculino , Ratos , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Interleucina-33/metabolismo , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Receptores de Interleucina-1 , Proteínas rho de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/genéticaRESUMO
Doxorubicin and platinum are widely used in the frontline treatment of osteosarcoma, but resistance to chemotherapy limits its curative effect. Here, we have identified that METTL1 mediated N7-Methyladenosine (m7G) low expressed in osteosarcoma tissues, plays a critical oncogenic role, and enhances osteosarcoma chemosensitivity in osteosarcoma. Mechanistically, AlkAniline-Seq data revealed that Ferritin heavy chain (FTH1), the main component of ferritin, which is crucial for iron homeostasis and the inhibition of lipid peroxidation, is one of the top 10 genes with the most significant change in m7G methylation sites mediated by METTL1 in human osteosarcoma cells. Interestingly, METTL1 significantly increased the expression of FTH1 at the mRNA level but was remarkably suppressed at the protein level. We then identified primary (pri)-miR-26a and pri-miR-98 in the Top 20 m7G-methylated pri-miRNAs with highly conserved species. Further results confirmed that METTL1 enhances cell ferroptosis by targeting FTH1 and primary (pri)-miR-26a, promoting their maturity by enhancing RNA stability dependent on m7G methylation. The increase of mature miR-26a-5p that resulted from METTL1 overexpression could further target FTH1 mRNA and eliminate FTH1 translation efficiency. Moreover, the reduction of FTH1 translation dramatically increases cell ferroptosis and promotes the sensitivity of osteosarcoma cells to chemotherapy drugs. Collectively, our study demonstrates the METTL1/pri-miR-26a/FTH1 axis signaling in osteosarcoma and highlights the functional importance of METTL1 and m7G methylation in the progression and chemotherapy resistance of osteosarcoma, suggesting that reprogramming RNA m7G methylation as a potential and promising strategy for osteosarcoma treatment.
Assuntos
Neoplasias Ósseas , Ferroptose , MicroRNAs , Osteossarcoma , Humanos , Ferroptose/genética , MicroRNAs/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , RNA Mensageiro , Ferritinas , Oxirredutases/metabolismoRESUMO
BACKGROUND: Special AT rich sequence binding protein 1 (SATB1) plays a crucial role in the biology of various types of human cancer. However, the role of SATB1 in human nasopharyngeal carcinoma (NPC) remains unknown. In the present study, we sought to investigate the contribution of aberrant SATB1 expression in the progression of NPC and its association with the Epstein Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1). METHODS: Immunohistochemical analysis was performed to detect SATB1 and LMP-1 protein in clinical samples, and the association of SATB1 protein expression with patient clinicopathological characteristics and LMP-1 expression were analyzed. SATB1 expression profiles were evaluated in well-differentiated NPC cell line CNE1, poorly-differentiated CNE2Z, undifferentiated C666-1 and immortalized nasopharyngeal epithelia NP-69 cells using quantitative RT-PCR, western blotting and fluorescent staining. After inhibition the SATB1 expression by using SATB1 specific small interfering RNA in these cell lines, the change of cell proliferation was investigated by western blotting analysis of PCNA (proliferating cell nuclear antigen) expression and CCK-8 assay, and the cell migration was assessed by Transwell migration assay. Finally, the expressions of SATB1 and PCNA were examined in CNE1 cells that forced LMP-1 expression by fluorescent staining and RT-PCR. RESULTS: Immunohistochemical analysis revealed that SATB1 protein expression was elevated in NPC tissues compared to benign nasopharyngeal tissues (P = 0.005). Moreover, high levels of SATB1 protein expression were positively correlated with clinical stage (P = 0.025), the status of lymph node metastasis (N classification) (P = 0.018), distant metastasis (M classification) (P = 0.041) and LMP-1 expression status (r = 2.35, P < 0.01) in NPC patients. In vitro experiments demonstrated that an inverse relationship between SATB1 expression and NPC differentiation status, with SATB1 weakly expressed in NP-69 cells and CNE1 cells, and significant increasingly expressed in CNE-2Z and C666-1 cells. Targeted knockdown of SATB1 expression obviously attenuated the proliferation and migration of highly SATB1-expressing CNE2Z and C666-1 cells, but not NP-69 and CNE1 cells. Interestingly, forced LMP-1 expression in CNE1 cells led to a surprisingly increasing SATB1 expression and nuclear location, companying with an up-regulated PCNA expression. CONCLUSIONS: Our results reveal that EBV LMP-1-mediated over-expression of SATB1 is associated with NPC progression, suggesting SATB1 may represent a promising biomarker and therapeutic target for NPC.
Assuntos
Progressão da Doença , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Proteínas da Matriz Viral/metabolismo , Adulto , Idoso , Carcinoma , Linhagem Celular Tumoral , Movimento Celular/genética , Núcleo Celular/metabolismo , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/genética , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Adulto JovemRESUMO
BACKGROUND: Overexpression of ubiquitin-conjugating enzyme 2C (UBE2C) has been detected in many types of human cancers, and is correlated with tumor malignancy. However, the role of UBE2C in human nasopharyngeal carcinoma (NPC) is unclear. In this study, we investigated the role of aberrant UBE2C expression in the progression of human NPC. METHODS: Immunohistochemical analysis was performed to detect UBE2C protein in clinical samples of NPC and benign nasopharyngeal tissues, and the association of UBE2C expression with patient clinicopathological characteristics was analyzed. UBEC2 expression profiles were evaluated in cell lines representing varying differentiated stages of NPC and immortalized nasopharyngeal epithelia NP-69 cells using quantitative RT-PCR, western blotting and fluorescent staining. Furthermore, UBE2C was knocked down using RNA interference in these cell lines and proliferation and cell cycle distribution was investigated. RESULTS: Immunohistochemical analysis revealed that UBE2C protein expression levels were higher in NPC tissues than in benign nasopharyngeal tissues (P<0.001). Moreover, high UBE2C protein expression was positively correlated with tumor size (P=0.017), lymph node metastasis (P=0.016) and distant metastasis (P=0.015) in NPC patients. In vitro experiments demonstrated that UBE2C expression levels were inversely correlated with the degree of differentiation of NPC cell lines, whereas UBE2C displayed low level of expression in NP-69 cells. Knockdown of UBE2C led to significant arrest at the S and G2/M phases of the cell cycle, and decreased cell proliferation was observed in poorly-differentiated CNE2Z NPC cells and undifferentiated C666-1 cells, but not in well-differentiated CNE1 and immortalized NP-69 cells. CONCLUSIONS: Our findings suggest that high expression of UBE2C in human NPC is closely related to tumor malignancy, and may be a potential marker for NPC progression.
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Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Progressão da Doença , Neoplasias Nasofaríngeas/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Adulto , Idoso , Carcinoma/secundário , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Nasofaringe/metabolismo , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
RATIONALE: Adenosquamous carcinoma of the scrotum is a rare cancer associated with poor prognosis. It is diagnosed through the presence of both adenocarcinoma and squamous cell carcinoma. PATIENT CONCERNS: It may be difficult to diagnose at early stages and may have poor survival. DIAGNOSES: We report a case of adenosquamous carcinoma of the scrotum in a 58-year-old male patient who presented with left scrotal mass for >1 year. INTERVENTIONS: This is the first case in the literature of primary adenosquamous carcinoma of the scrotum managed successfully with surgery and post-surgery chemotherapy and radiotherapy. OUTCOMES: The patient remained disease-free for 10 months postoperatively. LESSONS: The surgery treatment combined with postoperative radiotherapy and chemotherapy can improve the survival of adenosquamous carcinoma.
Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Carcinoma de Células Escamosas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Adenoescamoso/patologia , Escroto/patologia , Carcinoma de Células Escamosas/patologia , Prognóstico , Adenocarcinoma/patologiaRESUMO
Heart failure (HF) patients in general have a higher risk of developing cancer. Several animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression, highlighting a cause-and-effect relationship between these two disease entities. Targeting ferroptosis, a prevailing form of non-apoptotic cell death, has been considered a promising therapeutic strategy for human cancers. Exosomes critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine manner. However, whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been explored. Here, we demonstrate that myocardial infarction (MI) decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft tumor. Post-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis model. The expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as well. Incubation of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in vitro. Cardiomyocyte-enriched miR-22-3p was packaged in exosomes and transferred into tumor cells. Inhibition of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ferroptosis. ACSL4, a pro-ferroptotic gene, was experimentally established as a target of miR-22-3p in tumor cells. Taken together, our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from cardiomyocytes. Therefore, targeting exosome-mediated cardiomyocyte/tumor pathological communication may offer a novel approach for the ferroptosis-based antitumor therapy.
Assuntos
Exossomos , Ferroptose , Insuficiência Cardíaca , MicroRNAs , Infarto do Miocárdio , Neoplasias , Humanos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ferroptose/genética , Exossomos/metabolismo , Infarto do Miocárdio/genética , Neoplasias/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologiaRESUMO
Background: Cue-induced craving is widely considered to be the most important risk factor for relapse during abstinence from methamphetamine (Meth). There is limited research regarding electroencephalography (EEG) microstates of Meth-dependent patients under exposure to drug-related cues. Our objective was to investigate whether EEG microstate temporal characteristics could capture neural correlates of cue-induced Meth craving in virtual reality (VR) environments. Methods: EEG recordings of 35 Meth-dependent patients and 30 healthy controls (HCs) were collected during eyes-open state and cue-induced state, respectively. Group differences and condition differences in temporal parameters of four microstate classes were compared. Results: The results demonstrated the greater presence of microstate B in both Meth-dependent patients and HCs during the cue-induced condition, compared to resting state. In addition, for Meth-dependent patients, microstate C occurred significantly less frequently, along with a tendency of increased occurrence for class D during the cue-induced condition, compared to resting state. However, the change direction of class C and class D in HCs was completely opposite to that of Meth-dependent patients. The cue-induced condition also elicited different changes in transition probability between Meth-dependent patients and HCs. Conclusion: This study explored the features of EEG microstates in Meth-dependent patients during the cue-induced condition, which can improve our understanding of Meth addiction and contribute to the development of effective assessments and intervention tools.
RESUMO
We report a case of a 50-year-old woman presenting with a solid nodule in each lung. She was previously suspected of having lung cancer and distant pulmonary metastasis on the basis of imaging findings. Surgical pathology revealed that the left lung nodule was adenocarcinoma, but the contralateral nodule was papillary thyroid carcinoma (PTC). We subsequently performed total thyroidectomy, and the histological findings of the resected specimen showed no suspicious tumor tissue. Overall, the results led to a diagnosis of ectopic intrapulmonary PTC with synchronous lung adenocarcinoma. Ectopic intrapulmonary PTC is a rare but true phenomenon that may be easily mistaken for pulmonary metastasis in daily practice. It is important to improve the recognition of ectopic intrapulmonary thyroid tumors to avoid misdiagnosis.
Assuntos
Carcinoma Papilar , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
Background: Social cognition and interaction training (SCIT) is a psychosocial intervention program for patients with psychosis, designed to improve their social functioning by improving social cognition. Although the feasibility and efficacy of SCIT have been verified, patients with schizophrenia tend to suffer from motivational deficits and low treatment adherence. It has been suggested that using virtual reality (VR) technology might be effective in addressing these issues. In this study, we aimed to develop a VR-based SCIT and compare its efficacy with that of traditional SCIT. Materials and methods: We developed a novel VR-based social cognition and interaction training (VR-SCIT) that combines traditional SCIT (TR-SCIT) intervention with VR technology. Participants were randomly assigned in a 1:1:1 ratio to the VR-SCIT (n = 28), TR-SCIT (n = 30), or waiting-list groups (n = 29). All treatments were combined with treatment-as-usual. Assessments of social cognition (i.e., Chinese version of Face-Affective Identification Task, Chinese version of Social Cognition Screening Questionnaire) and social functioning (i.e., Chinese version of Personal and Social Performance Scale) were administered from baseline to post-intervention. Results: Patients receiving VR-SCIT and TR-SCIT showed a significantly greater improvement on the assessments of emotion perception (Cohen's d was 1.66, 0.55, and 0.10 for VR-SCIT, TR-SCIT, and Waiting-list, respectively), hostile attributional bias (Cohen's d was 0.48, 0.44, and 0.05 for VR-SCIT, TR-SCIT, and Waiting-list, respectively), metacognition (Cohen's d was 1.66, 0.76, and 0.06 for VR-SCIT, TR-SCIT, and waiting-list, respectively), and social functioning (Cohen's d was 1.09, 0.90, and 0.20 for VR-SCIT, TR-SCIT, and waiting-list, respectively) from baseline to post-intervention, compared to those in waiting-list group. Additionally, VR-SCIT showed an advantage over TR-SCIT in improving emotion perception and metacognition with higher treatment compliance. Conclusion: These preliminary findings indicate that VR-SCIT is a feasible and promising method for improving social cognition and social functioning in patients with schizophrenia.
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A new kind of temperature sensor based on a vacuum diode was proposed and numerically studied in this paper. This device operated under different electron emission mechanisms according to the electron density in the vacuum channel. The temperature determination ability of this device was only empowered when working in the electric-field-assisted thermionic emission regime (barrier-lowering effect). The simulated results indicated that the temperature-sensing range of this device was around 273 K-325 K with a supply current of 1 µA. To obtain a linear dependency of voltage on temperature, we designed a proportional-to-absolute-temperature (PTAT) circuit. The mathematic derivation of the PTAT voltage is presented in this study. The temperature-sensing sensitivity was calculated as 7.6 mV/K according to the measured I-U (current versus voltage) characteristic. The structure and principle of the device presented in this paper might provide an alternative method for the study of temperature sensors.
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Following the publication of this article, the authors have realized that they mistakenly used the total AKT blot featured in Fig. 4A for the GAPDH blot in Fig. 3B on p. 116. The corrected version of Fig. 3, featured the correct data for the GAPDH experiment, is shown opposite. The authors regret that this error was not picked up upon before the paper was sent to press, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish a corrigendum. The error did not affect either the results or the conclusions reported in the study, and all the authors agree to this corrigendum. Furthermore, they regret any inconvenience caused to the readership. [the original article was published in International Journal of Molecular Medicine 34: 112118, 2014; DOI: 10.3892/ijmm.2014.1773].
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Background: Laminin subunit gamma 1 (LAMC1) protein is associated with tumor cell invasion and metastasis. However, its role in kidney cancer remains unclear. In this work, we sought to probe the expression as well as its carcinogenic mechanisms of LAMC1 in kidney renal papillary cell carcinoma (KIRP) and kidney renal clear cell carcinoma (KIRC). Methods: Public databases including TIMER, Oncomine, UALCAN, TISIDB, TCGA, Kaplan-Meier plotter, UCSC Xena, cBioPortal, SurvivalMeth, KEGG, GeneMANIA, Metascape, GSCALite and GDSC were adopted, and the expression, clinical pathological correlation, prognostic signatures, dominant factors influencing LAMC1 expression, DNA methylation levels, gene mutations, copy number variations, functional networks, and drug sensitivity were analyzed. Expression of LAMC1 protein in clinical KIRP and KIRC was validated using tissue array. Results: LAMC1 expression in KIRP and KIRC were significantly higher than those in normal tissues. High LAMC1 expression indicated poor overall survival in KIRP patients and better overall survival in KIRC patients. Through the univariate and multivariate Cox analysis, we found that high LAMC1 expression was a potential independent marker for poor prognosis in KIRP, however it implied a better prognosis in KIRC by univariate Cox analysis. In addition, the LAMC1 expression in KIRP and KIRC was negatively correlated with methylation levels of LAMC1 DNA. Interestingly, LAMC1 expression was positively correlated with the infiltration of CD8+ T cells, dendritic cells and neutrophils in KIRP; however, it was positively correlated with the infiltration of CD4+ T cells, macrophages and neutrophils but negatively correlated with B cells in KIRC. Moreover, high level of CD8+ T cells is beneficial for KIRC prognosis but opposite for KIRP. LAMC1 may participate in signaling pathways involved in formation of adherens junction and basement membrane in KIRP and KIRC, and the high expression of LAMC1 is resistant to most drugs or small molecules of the Genomics of Drug Sensitivity in Cancer database. Conclusion: Enhanced LAMC1 expression suggests a poor prognosis in KIRP while a better prognosis in KIRC, and these opposite prognostic signatures of LAMC1 may be related to different immune microenvironments.