RESUMEN
Although LINC00313 is dysregulated in several tumors, its role in head and neck squamous cell carcinoma (HNSC) is not fully understood. The aim of this study was to analyze the role of LINC00313 in HNSC. The clinical information and LINC00313 expression data of HNSC were mined from the TCGA/GEO/cbioportal database. The correlation between LINC00313 expression and immune cell infiltration in HNSC tumors was analyzed by bioinformatics and gene enrichment analysis was performed. LINC00313 was silenced in HNSC cell lines, and changes at the genetic and molecular levels were verified through qRT-PCR and Western blotting. The researchers also validated its functional phenotype through a series of cell function experiments. The results showed that overexpression and copy number variation of LINC00313 in HNSC were associated with poorer prognosis. In addition, LINC00313 expression was significantly negatively correlated with immune cell infiltration. Silencing of LINC00313 in HNSC cells significantly reduced the rate of cell migration. LINC00313 may affect the progression of HNSC by regulating epithelial-mesenchymal transition. In conclusion, LINC00313 is a potential biomarker of HNSC prognosis and a potential target for immunotherapy.
Asunto(s)
Variaciones en el Número de Copia de ADN , Neoplasias de Cabeza y Cuello , Humanos , Biomarcadores , Transición Epitelial-Mesenquimal/genética , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , ARN Largo no CodificanteRESUMEN
BACKGROUND: Head and neck squamous carcinoma (HNSC) is a prevalent global malignancy with limited treatment options, which necessitates the development of novel therapeutic strategies. Disulfidptosis, a recently discovered and unique cell death pathway, may offer promise as a treatment target in HNSC. MATERIALS AND METHODS: We identified disulfidptosis-related genes (DRGs) using multiple algorithms and developed a prognostic model based on a disulfidptosis-related gene index (DRGI). The model's predictive accuracy was assessed by ROC-AUC, and patients were stratified by risk scores. We investigated the tumor immune microenvironment, immune responses, tumorigenesis pathways, and chemotherapy sensitivity (IC50). We also constructed a diagnostic model using 20 machine-learning algorithms and validated PCBP2 expression through RT-qPCR and western blot. RESULTS: We developed a 12-DRG DRGI prognostic model, classifying patients into high- and low-risk groups, with the high-risk group experiencing poorer clinical outcomes. Notable differences in tumor immune microenvironment and chemosensitivity were observed, with reduced immune activity and suboptimal treatment responses in the high-risk group. Advanced machine learning and in-vitro experiments supported DRGI's potential as a reliable HNSC diagnostic biomarker. CONCLUSION: We established a novel DRGI-based prognostic and diagnostic model for HNSC, exploring its tumor immune microenvironment implications, and offering valuable insights for future research and clinical trials.
RESUMEN
ENY2 (Enhancer of yellow 2 transcription factor) is a transcription nuclear protein and primarily participates in the course of mRNA export and histone deubiquitination to influence gene expression. Current studies have shown that the expression of ENY2 is significantly upregulated in multiple cancers. However, the exact association between ENY2 and pan-cancers has not been fully established. Here, we comprehensively analyzed ENY2 from the online public database and The Cancer Genome Atlas (TCGA) database, including gene expression level in pan-cancer, comparison of ENY2 expression in different molecular and immune subtypes of pan-cancer, targeted protein, biological functions, molecular signatures, diagnostic and prognostic value in pan-cancer. Moreover, we focused on head and neck squamous cell carcinoma (HNSC) and explored ENY2 from the perspective of the correlations with clinical characteristics, prognosis, co-expression genes, differentially expressed genes (DEGs) and immune Infiltration. Our findings showed that the expression of ENY2 differed enormously not only in most cancer types but also in different molecular and immune subtypes of cancers. High accuracy in predicting cancers and notable correlations with prognosis of certain cancers suggested that ENY2 might be a potential diagnostic and prognostic biomarker of cancers. In addition, ENY2 was identified to be significantly correlated with clinical stage, gender, histologic grade and lymphovascular invasion in HNSC. Overexpression of ENY2 could lead to a worse overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HNSC, especially in different clinical subgroups of HNSC. Taken together, ENY2 showed strong correlation with the diagnosis and prognosis of pan-cancer, and was an independent prognostic risk factor of HNSC, which may serve as a potential target for cancer management.
Asunto(s)
Neoplasias de Cabeza y Cuello , Secuencias Reguladoras de Ácidos Nucleicos , Humanos , Biomarcadores , Neoplasias de Cabeza y Cuello/genética , Proteínas Nucleares , Procesamiento Proteico-Postraduccional , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
BACKGROUND: The establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the development of multiple malignancies. However, its role in hypopharyngeal carcinoma (HPC) progression remains uncharacterized. METHODS: This study employed bioinformatics to determine the ESCO2 expression in head and neck squamous cell carcinoma (HNSC) and normal tissues. In vitro cell proliferation, migration, apoptosis, and/or cell cycle distribution assays were used to determine the function of ESCO2 and its relationship with STAT1. Xenograft models were established in nude mice to determine ESCO2 in HPC growth in vivo. Co-immunoprecipitation/mass spectrometry (Co-IP/MS) was conducted to identify the potential ESCO2 binding partners. RESULTS: We found that ESCO2 expression was elevated in HNSC tissues, and ESCO2 depletion suppressed tumor cell migration in vitro and inhibited tumor growth in vitro and in vivo. Co-IP/MS and immunoblotting assays revealed the interaction between ESCO2 and STAT1 in HPC cells. STAT1-overexpression compromised ESCO2-mediated suppressive effects on HPC cell proliferation, viability, and migration. CONCLUSIONS: These findings suggest that ESCO2 is crucial in promoting HPC malignant progression through the STAT1 pathway and provides novel therapeutic targets for HPC treatment.
Asunto(s)
Segregación Cromosómica , Neoplasias de Cabeza y Cuello , Animales , Ratones , Humanos , Ratones Desnudos , Proliferación Celular , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Línea Celular Tumoral , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Acetiltransferasas/genética , Proteínas Cromosómicas no Histona/genéticaRESUMEN
Head and neck squamous carcinoma (HNSC) poses a significant public health challenge due to its substantial morbidity. Nevertheless, despite advances in current treatments, the prognosis for HNSC remains unsatisfactory. To address this, single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies were conducted to examine the role of MYO5A (Myosin VA) in HNSC. Our investigation revealed an overexpression of MYO5A in HNSC that promotes HNSC migration in vitro. Remarkably, knockdown of MYO5A suppressed vimentin expression. Furthermore, analyzing the TCGA database evidenced that MYO5A is a risk factor for human papillomavirus positive (HPV+) HNSC (HR = 0.81, P < 0.001). In high MYO5A expression HNSC, there was a low count of tumor infiltrating lymphocytes (TIL), including activated CD4+ T cells, CD8+ T cells, and B cells. Of note, CD4+ T cells and B cells were positively associated with improved HPV+ HNSC outcomes. Correlation analysis demonstrated a decreased level of immunostimulators in high MYO5A-expressing HNSC. Collectively, these findings suggest that MYO5A may promote HNSC migration through vimentin and involve itself in the process of immune infiltration in HNSC, advancing the understanding of the mechanisms and treatment of HNSC.
Asunto(s)
Neoplasias de Cabeza y Cuello , Miosina Tipo V , Infecciones por Papillomavirus , Humanos , Vimentina/genética , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Procesos Neoplásicos , Pronóstico , Linfocitos Infiltrantes de Tumor , Cadenas Pesadas de Miosina/genética , Miosina Tipo V/genéticaRESUMEN
BACKGROUND: Sulfatase gene family members mediate various biological functions in tumor stroma and tumor cell environments. However, the expressions and prognostic value of Arylsulfatase I (ARSI), a sulfatase gene family member, in head and neck squamous cell carcinoma (HNSC) have not been fully established. METHODS: Arylsulfatase I expressions in pan-cancer were profiled using publicly available databases. Then, univariate Cox regression, Kaplan-Meier, and the Pearson's correlation analyses were performed to determine correlations between ARSI expressions and cancer prognosis, immune cell status, and drug sensitivity. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were used to assess the potential mechanisms underlying ARSI functions in HNSC. RESULTS: Arylsulfatase I was highly expressed in 15 cancer types, with significant expressions in HNSC. Elevated ARSI levels were associated with worse prognostic outcomes in HNSC patients. In addition, GSVA and GSEA showed that ARSI was highly involved in tumor cell escape and inflammatory responses. Expressions of ARSI negatively correlated with tumor mutation burden or microsatellite instability and positively correlated with immune-related genes. Elevated ARSI expressions conferred poor tolerance to daporinad and sinularin, but increased cell sensitivity to dasatinib and XAV939. CONCLUSION: Arylsulfatase I is a promising prognostic and therapeutic target for HNSC.
Asunto(s)
Neoplasias de Cabeza y Cuello , Arilsulfatasas , Biomarcadores de Tumor/metabolismo , Neoplasias de Cabeza y Cuello/genética , Humanos , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , SulfatasasRESUMEN
This study aimed to screen the key immune-related genes (IRGs) in head and neck squamous cell carcinoma (HNSC) and construct the IRGs-related prognostic model to predict the overall survival (OS) of patients with HNSC. The RNA-seq data and clinical data were downloaded from The Cancer Genome Atlas database, and IRGs were obtained from the Immunology Database and Analysis Portal. Differentially expressed genes (DEGs) between HNSC and normal samples were identified, followed by integration with IRGs to screen differentially expressed IRGs. After univariate and multivariate proportional hazard regression analyses, an IRG-based risk model was constructed. Meanwhile, data chip of GSE65858 as the validation set to assess the predicted performance of established model. Next, univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factor of HNSC, and the Nomogram model was developed to predict patient outcome. Furthermore, the correlation between immune cell infiltration and risk score was analyzed. A total of 65 differently expressed IRGs associated with prognosis of HNSC were screened, and finally a 26-gene IRG signature was identified to construct a prognostic prediction model. The AUC of ROC curve was 0.750. Survival analysis showed that patients in the high-risk group had a worse prognosis. Independent prognostic analysis showed that risk score could be considered as an independent predictor for HNSC prognosis. Nomogram assessment showed that the model had high reliability for predicting the survival of patients with HNSC in 1, 2, 3 years. Ultimately, the abundance of B cells and CD4+ T cell infiltration in HNSC showed negative correlations with risk score. Our IRG-based prognostic risk model may be used to estimate the prognosis of HNSC patients.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , Biomarcadores de Tumor/genética , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/genética , Humanos , Pronóstico , Reproducibilidad de los ResultadosRESUMEN
Receptor tyrosine kinases (RTK) are rarely mutated in cutaneous melanoma, but the expression and activation of several RTK family members are associated with a proinvasive phenotype and therapy resistance. Epidermal growth factor receptor (EGFR) is a member of the RTK family and is only expressed in a subgroup of melanomas with poor prognosis. The insight into regulators of EGFR expression and activation is important for the understanding of the development of this malignant melanoma phenotype. Here, we describe that the transcription factor NRF2, the master regulator of the oxidative and electrophilic stress response, mediates the expression and activation of EGFR in melanoma by elevating the levels of EGFR as well as its ligands EGF and TGFα. ChIP sequencing data show that NRF2 directly binds to the promoter of EGF, which contains a canonical antioxidant response element. Accordingly, EGF is induced by oxidative stress and is also increased in lung adenocarcinoma and head and neck carcinoma with mutationally activated NRF2. In contrast, regulation of EGFR and TGFA occurs by an indirect mechanism, which is enabled by the ability of NRF2 to block the activity of the melanocytic lineage factor MITF in melanoma. MITF effectively suppresses EGFR and TGFA expression and therefore serves as link between NRF2 and EGFR. As EGFR was previously described to stimulate NRF2 activity, the mutual activation of NRF2 and EGFR pathways was investigated. The presence of NRF2 was necessary for full EGFR pathway activation, as NRF2-knockout cells showed reduced AKT activation in response to EGF stimulation compared to controls. Conversely, EGF led to the nuclear localization and activation of NRF2, thereby demonstrating that NRF2 and EGFR are connected in a positive feedback loop in melanoma. In summary, our data show that the EGFR-positive melanoma phenotype is strongly supported by NRF2, thus revealing a novel maintenance mechanism for this clinically challenging melanoma subpopulation.
Asunto(s)
Melanoma/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Elementos de Respuesta Antioxidante , Secuencia de Bases , Sitios de Unión , Biomarcadores de Tumor , Proteínas Portadoras , Línea Celular Tumoral , Receptores ErbB/metabolismo , Humanos , Estimación de Kaplan-Meier , Ligandos , Melanoma/etiología , Melanoma/mortalidad , Melanoma/patología , Modelos Biológicos , Motivos de Nucleótidos , Unión ProteicaRESUMEN
BACKGROUND: Head and neck squamous cell carcinoma (HNSC) ranks as the sixth most common malignancy. The identification of highly specific and sensitive prognostic markers and potential drug targets can contribute to enhanced patient prognosis and individualized treatments. Heat shock proteins (HSPs) act as molecular chaperones and play a crucial role in maintaining cell homeostasis. Recently, research has indicated that HSPs also act as "evil chaperones" in cancer development. METHODS: In this study, we assessed the expression of HSPs in HNSC patients using the ONCOMINE, GEPIA, and UALCAN databases. Mutations of HSP genes were also analysed using the cBioPortal database. Additionally, the expression levels of HSPs were verified using the Human Protein Altas (THPA) database. RESULTS: We found that the expression levels of HSPH1, HSPD1, SERPINH1, HSPA4, and HSP90AA1 were significantly higher in tissues from HNSC patients compared with normal tissues. Moreover, HSPH1, HSPD1, SERPINH1, HSPA4 and HSP90AA1 expressions were linked to disease progression. Survival analysis with the GEPIA and OncoLnc databases indicated that upregulation of HSPH1, HSPD1, SERPINH1, HSPA4 and HSP90AA1 was related to poor overall survival (OS). CONCLUSION: This study suggests that the HSPH1, HSPD1, SERPINH1, HSPA4 and HSP90AA1 genes are potential clinical targets and prognostic biomarkers for patients with HNSC.
RESUMEN
miR-18a is a member of primary transcript called miR-17-92a (C13orf25 or MIR17HG) which also contains five other miRNAs: miR-17, miR-19a, miR-20a, miR-19b and miR-92a. This cluster as a whole shows specific characteristics, where miR-18a seems to be unique. In contrast to the other members, the expression of miR-18a is additionally controlled and probably functions as its own internal controller of the cluster. miR-18a regulates many genes involved in proliferation, cell cycle, apoptosis, response to different kinds of stress, autophagy and differentiation. The disturbances of miR-18a expression are observed in cancer as well as in different diseases or pathological states. The miR-17-92a cluster is commonly described as oncogenic and it is known as 'oncomiR-1', but this statement is a simplification because miR-18a can act both as an oncogene and a suppressor. In this review we summarize the current knowledge about miR-18a focusing on its regulation, role in cancer biology and utility as a potential biomarker.
RESUMEN
A large number of treatment approaches have been used for spinal cord injury improvement, a medically incurable disorder, and subsequently stem cell transplantation appears to be a promising strategy. The main objective of this study is to ascertain whether combinational therapy of human neural stem cells (hNSCs) together with lithium chloride improves cell survival, proliferation, and differentiation in a rat spinal contusion model, or not. Contusive spinal cord injury was implemented on Wistar male rats. Experimental groups comprised of: control, hNSCs transplanted, lithium chloride (Li), and hNSCs and lithium chloride (hNSCs + Li). In every experimental group, locomotor activity score and motor evoked potential (MEP) were performed to evaluate motor recovery as well as histological assessments to determine mechanisms of improvement. In accordance with our results, the hNSCs + Li and the Li groups showed significant improvement in locomotor scores and MEP. Also, Histological assessments revealed that transplanted hNSCs are capable of differentiation and migration along the spinal cord. Although NESTIN-positive cells were proliferated significantly in the Lithium group in comparison with control and the hNSCs + Li groups, the quantity of ED1 cells in the hNSCs + Li was significantly larger than the other two groups. Our results demonstrate that combinational therapy of hNSCs with lithium chloride and lithium chloride individually are adequate for ameliorating more than partial functional recovery and endogenous repair in spinal cord-injured rats.
Asunto(s)
Litio/uso terapéutico , Células-Madre Neurales/trasplante , Traumatismos de la Médula Espinal/terapia , Trasplante de Células Madre , Animales , Conducta Animal , Diferenciación Celular , Movimiento Celular , Supervivencia Celular , Terapia Combinada , Modelos Animales de Enfermedad , Potenciales Evocados Motores , Humanos , Macrófagos/patología , Masculino , Actividad Motora , Ratas Wistar , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatología , Cicatrización de HeridasRESUMEN
Numerous chemicals including environmental toxicants and drugs have not been fully evaluated for developmental neurotoxicity. A key gap exists in the ability to predict accurately and robustly in vivo outcomes based on in vitro assays. This is particularly the case for predicting the toxicity of chemicals on the developing human brain. A critical need for such in vitro assays is choice of a suitable model cell type. To that end, we have performed high-throughput in vitro assessment of proliferation and differentiation of human neural stem cells (hNSCs). Conventional in vitro assays typically use immunofluorescence staining to quantify changes in cell morphology and expression of neural cell-specific biomarkers, which is often time-consuming and subject to variable specificities of available antibodies. To alleviate these limitations, we developed a miniaturized, three-dimensional (3D) hNSC culture with ReNcell VM on microarray chip platforms and established a high-throughput promoter-reporter assay system using recombinant lentiviruses on hNSC spheroids to assess cell viability, self-renewal, and differentiation. Optimum cell viability and spheroid formation of 3D ReNcell VM culture were observed on a micropillar chip over a period of 9 days in a mixture of 0.75% (w/v) alginate and 1â¯mg/mL growth factor reduced (GFR) Matrigel with 25â¯mM CaCl2 as a crosslinker for alginate. In addition, 3D ReNcell VM culture exhibited self-renewal and differentiation on the microarray chip platform, which was efficiently monitored by enhanced green fluorescent protein (EGFP) expression of four NSC-specific biomarkers including sex determining region Y-box 2 (SOX2), glial fibrillary acidic protein (GFAP), synapsin1, and myelin basic protein (MBP) with the promoter-reporter assay system.
Asunto(s)
Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Células-Madre Neurales/metabolismo , Neuronas/citología , Técnicas de Cultivo de Célula/métodos , Supervivencia Celular/fisiología , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Análisis por Matrices de Proteínas/métodosRESUMEN
AIM: This study aimed to identify PFN2 expression profile, its prognostic value and the mechanism of its dysregulation in head and neck squamous cell carcinoma (HNSC). MATERIALS & METHODS: Bioinformatic analysis was performed using data in the Gene Expression Omnibus Datasets, Human Protein Atlas and The Cancer Genome Atlas-HNSC. RESULTS: PFN2 was upregulated in HNSC than in normal head and neck tissues. High PFN2 expression independently predicted poor overall survival in primary HNSC (hazard ratio: 1.548, 95% CI: 1.174-2.042; p = 0.002). Fourteen percent of HNSC cases had PFN2 amplification. PFN2 DNA methylation was negatively correlated with its mRNA expression (Pearson's r = -0.713). CONCLUSION: High PFN2 expression might serve as a valuable predictor for poor overall survival of HNSC. DNA amplification and hypomethylation might be two mechanisms of PFN2 dysregulation.
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/mortalidad , Profilinas/genética , Anciano , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Biología Computacional/métodos , Metilación de ADN , Bases de Datos Genéticas , Femenino , Amplificación de Genes , Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Profilinas/metabolismo , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Análisis de SupervivenciaRESUMEN
In this study, we investigated whether there is any association between the expression of FSCN1 and SNAI2 and the possible underlying mechanisms in head and neck squamous cell carcinoma (HNSC). In addition, we also investigated whether FSCN1 modulates epithelial-to-mesenchymal transition (EMT) in HNSC cells. Microarray data of dysregulated genes in HNSC were searched in GEO datasets. The association between FSCN1 expression and the 5-year/10-year overall survival (OS), as well as the correlation between the expression of FSCN1 and SOX2, MYBL2, SNAI2, STAT1, and SOX4, was analyzed based on data in TCGA HNSC cohort (TCGA-HNSC). The binding site of SNAI2 in FSCN1 promoter was verified using luciferase reporter assay. SCC9 and SCC15 cells were transfected with pCMV-SNAI2 or pCMV-FSCN1 expression vector or the empty control. Alteration of E-cadherin, Claudin 1, Vimentin, and N-cadherin was then quantified. Our results showed that FSCN1 is significantly upregulated in HNSC tissues compared with the normal control tissues. High FSCN1 expression is associated with worse 5-year and 10-year OS among the HNSC patients. Bioinformatic prediction showed a highly possible SNAI2 binding site in FSCN1 promoter and following luciferase reporter assay verified this site. SNAI2 overexpression significantly increased FSCN1 expression at both mRNA and protein level. FSCN1 overexpression reduced the expression of E-cadherin and Claudin 1, but increased the expression of Vimentin and N-cadherin in SCC9 and SCC-15 cells. Therefore, we infer that FSCN1 is a downstream effector of SNAI2 in promoting EMT in HNSC cells.
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proteínas Portadoras/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Proteínas de Microfilamentos/genética , Factores de Transcripción de la Familia Snail/genética , Sitios de Unión , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Carcinoma de Células Escamosas/patología , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Claudina-1/metabolismo , Transición Epitelial-Mesenquimal , Células HEK293 , Neoplasias de Cabeza y Cuello/patología , Humanos , Proteínas de Microfilamentos/biosíntesis , Proteínas de Microfilamentos/metabolismo , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción de la Familia Snail/biosíntesis , Factores de Transcripción de la Familia Snail/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Factores de Transcripción/metabolismo , Activación Transcripcional , Regulación hacia Arriba , Vimentina/metabolismoRESUMEN
Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.
Asunto(s)
Biomarcadores de Tumor , Neoplasias de Cabeza y Cuello , Inmunoterapia , Procolágeno-Prolina Dioxigenasa , Humanos , Biomarcadores de Tumor/metabolismo , Pronóstico , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/diagnóstico , Inmunoterapia/métodos , Procolágeno-Prolina Dioxigenasa/metabolismo , Procolágeno-Prolina Dioxigenasa/genética , Regulación Neoplásica de la Expresión Génica , Femenino , Masculino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/mortalidadRESUMEN
Study finds that eukaryotic translation initiation factor 3 subunit D (EIF3D) may play an important role in aberrant alternative splicing (AS) events in tumors. AS possesses a pivotal role in both tumour progression and the constitution of the tumour microenvironment (TME). Regrettably, our current understanding of AS remains circumscribed especially in the context of immunogene-related alternative splicing (IGAS) profiles within Head and Neck Squamous Cell Carcinoma (HNSC). In this study, we comprehensively analyzed the function and mechanism of action of EIF3D by bioinformatics analysis combined with in vitro cellular experiments, and found that high expression of EIF3D in HNSC was associated with poor prognosis of overall survival (OS) and progression-free survival (PFS). The EIF3D low expression group had a higher degree of immune infiltration and better efficacy against PD1 and CTLA4 immunotherapy compared to the EIF3D high expression group. TCGA SpliceSeq analysis illustrated that EIF3D influenced differentially spliced alternative splicing (DSAS) events involving 105 differentially expressed immunogenes (DEIGs). We observed an induction of apoptosis and a suppression of cell proliferation, migration, and invasion in EIF3D knock-down FaDu cells. RNA-seq analysis unveiled that 531 genes exhibited differential expression following EIF3D knockdown in FaDu cells. These include 52 DEIGs. Furthermore, EIF3D knockdown influenced the patterns of 1923 alternative splicing events (ASEs), encompassing 129 IGASs. This study identified an RNA splicing regulator and revealed its regulatory role in IGAS and the TME of HNSC, suggesting that EIF3D may be a potential target for predicting HNSC prognosis and immunotherapeutic response.
Asunto(s)
Empalme Alternativo , Factor 3 de Iniciación Eucariótica , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factor 3 de Iniciación Eucariótica/genética , Factor 3 de Iniciación Eucariótica/metabolismo , Empalme Alternativo/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Pronóstico , Apoptosis/genética , Masculino , Movimiento Celular/genética , FemeninoRESUMEN
BACKGROUND: Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited. METHODS: UBE2T expression in HNSC patient samples and the correlation between its expression and patients' survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. RESULTS: The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling and induced ferroptosis in HNSC. CONCLUSION: Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target.
Asunto(s)
Ferroptosis , Técnicas de Silenciamiento del Gen , Neoplasias de Cabeza y Cuello , FN-kappa B , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello , Enzimas Ubiquitina-Conjugadoras , Enzimas Ubiquitina-Conjugadoras/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Ferroptosis/genética , Humanos , FN-kappa B/metabolismo , FN-kappa B/genética , Animales , Ratones , Línea Celular Tumoral , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Masculino , Progresión de la Enfermedad , Femenino , Ratones DesnudosRESUMEN
BACKGROUND: MicroRNA-584-5p (miR-584-5p) plays an important role in certain types of cancer. However, its precise role in head and neck squamous cell carcinoma (HNSC) remains unknown. OBJECTIVE: Our aim was to investigate how miR-584-5p influences HNSC. METHODS: The Cancer Genome Atlas (TCGA) provided samples for the study. We use statistical methods to evaluate the diagnostic value, the prognostic value, and the correlation with the clinical features of miR-584-5p. We analyze the target genes and the regulatory network of miR- 584-5p. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed the expression of miR- 584-5p in HNSC cell lines. RESULTS: MiR-584-5p expression of miR-584-5p varied significantly among different types of cancer. A notable correlation was observed between elevated miR-584-5p expression and gender (p < 0.001) and histological grade (p < 0.001). Furthermore, high levels of miR-584-5p were found to be associated with a decrease in overall survival (HR: 1.44; 95% CI: 1.10-1.88; p = 0.007), progression-free survival (HR: 1.35; 95% CI: 1.02-1.79; p = 0.035) and disease-specific survival (HR: 1.54; 95% CI: 1.09-2.18; p = 0.016) in the context of HNSC. miR-584-5p demonstrated independent prognostic significance in HNSC and potentially contributes to disease progression through multiple pathways, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In particular, HNSC cell lines exhibited a substantial upregulation of miR-584-5p compared to normal epithelial cells. CONCLUSIONS: It is possible that miR-584-5p could serve as a promising patent for a therapeutic target and prognostic biomarker for people with HNSC.
RESUMEN
OBJECTIVE: Angiogenesis-associated genes (AAGs) play a critical role in cancer patient survival. However, there are insufficient reports on the prognostic value of AAGs in head and neck squamous cell carcinoma (HNSC). Therefore, this study aimed to investigate the correlation between AAG expression levels and survival in HNSC patients, explore the predictive value of signature genes and lay the groundwork for future in-depth research. METHODS: Relevant data for HNSC were obtained from the databases. AAGs-associated signature genes linked to prognosis were screened to construct a predictive model. Further analysis was conducted to determine the functional correlation of the signature genes. RESULTS: The signature genes (STC1, SERPINA5, APP, OLR1, and PDGFA) were used to construct prognostic models. Patients were divided into high-risk and low-risk groups based on the calculated risk scores. Survival analysis showed that patients in the high-risk group had a significantly lower overall survival than those in the low-risk group (P < 0.05). Therefore, this prognostic model was an independent prognostic factor for predicting HNSC. In addition, patients in the low-risk group were more sensitive to multiple anti-cancer drugs. Functional correlation analysis showed a good correlation between the characteristic genes and HNSC metastasis, invasion, and angiogenesis. CONCLUSION: This study established a new prognostic model for AAGs and may guide the selection of therapeutic agents for HNSC. These genes have important functions in the tumor microenvironment; it also provides a valuable resource for the future clinical trials investigating the relationship between HNSC and AAGs.
RESUMEN
Background: Autophagy, a crucial cellular mechanism, facilitates the degradation and removal of misfolded proteins and impaired organelles. Recent research has increasingly highlighted the intimate connection between autophagy and heat shock proteins (HSPs) in the context of tumor development. However, the specific role and underlying mechanisms of heat shock protein 90 beta family member 1 (HSP90B1) in modulating autophagy within head and neck squamous cell carcinoma (HNSCC) remain elusive. Methods: Quantitative real-time PCR (qRT-PCR), Western blot (WB), immunohistochemistry (IHC) were used to detect the expression in HNSC cell lines and tissues. The relationship between HSP90B1 and clinicopathologic features was explored based on TCGA (The Cancer Genome Atlas) data and IHC results. The biological functions of HSP90B1 were analyzed through in vitro and in vivo models to evaluate proliferation, migration, invasion, and autophagy. The mechanisms of HSP90B1 were studied using bioinformatics and WB. Results: HSP90B1 was upregulated in HNSC cells and tissues. High HSP90B1 levels were associated with T-stage, M-stage, clinical stage, and poor prognosis in HNSC patients. Functionally, HSP90B1 promotes HNSC cell proliferation, migration, invasion and inhibits apoptosis. We discovered that HSP90B1 obstructs autophagy and advances HNSC progression through the PI3K/Akt/mTOR pathway. Conclusion: Our study demonstrates that HSP90B1 is highly expressed in HNSC. Furthermore, HSP90B1 may regulate autophagy through the PI3K/Akt/mTOR pathway, mediating HNSC cell biological behaviors. These provide new insights into potential biomarkers and targets for HNSC therapy.