RESUMEN
This study delves into the molecular intricacies of hypopharyngeal squamous cell carcinoma (HSCC), specifically focusing on the pivotal role played by ETS translocation variant 4 (ETV4) in aerobic glycolysis. The objective is to uncover new targets for early diagnosis and treatment of HSCC. ETV4 expression in HSCC tissues was rigorously examined, revealing its association with patient survival. Through comprehensive experimentation, we demonstrated that ETV4 activation promotes HSCC cell proliferation and invasion while inhibiting apoptosis. Furthermore, in vivo experiments confirmed the tumor-promoting effect of ETV4 activation. The study elucidated the binding of ETV4 to the NSUN2 promoter and its influence on PKM2 expression, thereby regulating glycolysis and cellular functions in HSCC.
RESUMEN
Allergic rhinitis (AR) is a common allergic disease. Cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) is a member of the cytochrome P450 family of enzymes, while its role in AR is still unveiled. In AR mice, T cell-specific overexpression of Cyp2e1 relieved the AR symptoms. Overexpressed-Cyp2e1 restrained the infiltration of eosinophils and mast cells in the nasal mucosa of mice, and the inflammatory cells in nasal lavage fluid (NALF). Cyp2e1 overexpressed mice exhibited decreased goblet cell hyperplasia and mucus secretion as well as decreased MUC5AC expression in nasal mucosa. The epithelial permeability and integrity of nasal mucosa were improved upon Cyp2e1 overexpression in AR mice, as evidenced by decreased fluorescein isothiocyanate-dextran 4 content in serum, increased expression of IL-25, IL-33, and TSLP in NALF, and increased expression of ZO-1 and occluding in nasal mucosa. Cyp2e1 inhibited Th2 immune response by decreasing the expression and secretion of IL-4, IL-5, and IL-13 as well as the expression of GATA-3 in NALF or nasal mucosa. We proved that Cyp2e1 inhibited the differentiation of naïve CD4+ T cells toward the Th2 subtype, which was regulated by MAFB by binding to Cyp2e1 promoter to activate its transcription. Overall, these results show the potential role of Cyp2e1 in alleviating AR symptoms by restraining CD4+ T cells to Th2 cell differentiation. Our findings provide further insight into the AR mechanism.
Asunto(s)
Diferenciación Celular , Citocromo P-450 CYP2E1 , Mucosa Nasal , Ovalbúmina , Rinitis Alérgica , Células Th2 , Animales , Humanos , Ratones , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP2E1/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Activación de Linfocitos , Ratones Endogámicos BALB C , Mucosa Nasal/inmunología , Mucosa Nasal/patología , Ovalbúmina/inmunología , Rinitis Alérgica/inmunología , Células Th2/inmunologíaRESUMEN
OBJECTIVES: Allergic rhinitis (AR) is an inflammatory autoimmune disease with disorder of the nasal mucosa. Cadherin 26 (CDH26), an alpha integrin-binding epithelial receptor, is regulated during allergic inflammation. This study aimed to investigate whether CDH26 contributes to the severity of AR. STUDY DESIGN: In vivo and in vitro. METHODS: We investigated the effects of CDH26 knockdown by lentivirus (LV)-mediated shRNA on ovalbumin (OVA)-induced AR mice and IL-13-stimulated human nasal epithelial cells (NECs). RESULTS: CDH26 mRNA and protein expression was significantly increased in the nasal mucosa of AR patients and mice. Intranasal instillation of LV-shCDH26 alleviated allergic symptoms and decreased the histological changes of nasal mucosa in AR mice. Furthermore, the serum levels of OVA-specific IgE, IgG, pro-inflammatory factors IL-25, IL-33, and TSLP were decreased in AR mice with CDH26 knockdown. With regard to AR-induced Th2 inflammation, LV-shCDH26 intervention effectively decreased the distribution of CD4+ /GATA3+ Th2 cells, and the mRNA expression of IL-4, IL-5, and IL-13 in the nasal mucosa. CDH26 knockdown down-regulated the expression of ß-catenin but not for E-cadherin and ZO-1 in nasal mucosa induced by AR. In vitro, CDH26 knockdown inhibited the protein expression of TSLP, GM-CSF and eotaxin in NECs, and CDH26 overexpression remarkably promoted the production of these inflammatory factors in IL-13-induced NECs. CONCLUSIONS: CDH26 knockdown attenuates the AR-induced inflammatory response both in vivo and in vitro. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1558-1567, 2023.
Asunto(s)
Cadherinas , Rinitis Alérgica , Animales , Humanos , Ratones , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inflamación , Interleucina-13 , Mucosa Nasal/patología , Rinitis Alérgica/genética , Rinitis Alérgica/patología , ARN Mensajero , Cadherinas/genéticaRESUMEN
Objective: Childhood obstructive sleep apnea hypopnea syndrome (OSAHS) is a common clinical disease that can cause serious complications if not treated in time. Adenoidectomy with or without tonsillectomy is the most important first line surgical treatment of obstructive sleep apnea in children. The aim of this study was to compare the differences between these two surgical procedures for adenoidectomy in terms of operation time, intraoperative blood loss, proportion of patients experiencing postoperative delayed hemorrhage, and incidence of adverse events. Study Design: Retrospective analysis. Methods: We performed a retrospective systematic analysis of patient data using the in-house electronic patient records and considered a 2-year period from 2016 to 2017. In total, 468 patients who underwent adenoidectomy under nasal endoscopy with coblation or microdebrider were identified. Results: The coblation adenoidectomy technique was associated with significantly reduced blood loss and operation time. However, incidence of fever, neck pain, and halitosis were significantly lower in the microdebrider adenoidectomy group (p < .01). The difference in the postoperative primary and secondary hemorrhage between the two groups was not statistically significant (p > .05). Conclusion: Coblation adenoidectomy had a significantly higher incidence of adverse events such as halitosis, neck pain, and fever. Therefore, otorhinolaryngologists should consider the differences in adverse events when selecting use of coblation adenoidectomy for pediatric patients. Level of Evidence: IV.
RESUMEN
PURPOSE: This work aimed to investigate the effects of MAF bZIP transcription factor B (MAFB) on the progression of allergic rhinitis (AR). PATIENTS AND METHODS: Nasal mucosa was isolated from AR patients and healthy individuals from Shengjing Hospital of China Medical University. The experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University (2019PS341K) in accordance with the Declaration of Helsinki. Informed consents were signed by participants or a parent/legal guardian of the participants under 18 years old of age. Then, an AR mouse model with MAFB overexpression was established with 25 µg ovalbumin (OVA) sensitization on day 0, 7, 14, followed by an injection with 1×107 TU/mL lentivirus MAFB on day 19 and a nasal challenge with 500 µg OVA from day 21 to 27. RESULTS: The results revealed that MAFB was down-regulated in the nasal mucosa of AR patients. The up-regulation of MAFB protected the AR mice against the OVA-induced allergic symptoms (sneezing and nasal rubbing) by alleviating the OVA-induced epithelial thicknesses, goblet cell hyperplasia, and inflammation including the eosinophil and mast cell infiltration. Moreover, MAFB facilitated the T helper (Th) 1 response and inhibited the Th2 and Th17 responses by the down-regulation of T-box transcription factor 21 and the up-regulation of GATA binding protein-3 as well as retinoid-related orphan receptor-γt in the splenocytes of AR mice. MAFB was found to repress the differentiation of naive CD4+ T cells into Th2 cells. Subsequently, MAFB overexpression reversed the OVA-induced enhancement of epithelial permeability, downregulation of tight junctions, and upregulation of cadherin-26, indicating the protective role of MAFB on epithelial barrier integrity. CONCLUSION: MAFB protected against OVA-induced AR via the alleviation of inflammation by restoring the Th1/Th2/Th17 imbalance and epithelial barrier dysfunction.
RESUMEN
Background: Transmembrane protein 16A (TMEM16A) Ca2+-activated Cl- channels have diverse physiological functions, such as epithelial secretion of Cl- and fluid and sensation of pain. Recent studies have demonstrated that TMEM16A contributes to the pathogenesis of infectious and non-infectious inflammatory diseases. However, the role of TMEM16A in inflammation has not been clearly elucidated. Aim of review: In this review, we aimed to provide comprehensive information regarding the roles of TMEM16A in inflammation by summarizing the mechanisms underlying TMEM16A expression and activation under inflammatory conditions, in addition to exploring the diverse inflammatory signaling pathways activated by TMEM16A. This review attempts to develop the idea that TMEM16A plays a diverse role in inflammatory processes and contributes to inflammatory diseases in a cellular environment-dependent manner. Key scientific concepts of review: Multiple inflammatory mediators, including cytokines (e.g., interleukin (IL)-4, IL-13, IL-6), histamine, bradykinin, and ATP/UTP, as well as bacterial and viral infections, promote TMEM16A expression and/or activity under inflammatory conditions. In addition, TMEM16A activates diverse inflammatory signaling pathways, including the IP3R-mediated Ca2+ signaling pathway, the NF-κB signaling pathway, and the ERK signaling pathway, and contributes to the pathogenesis of many inflammatory diseases. These diseases include airway inflammatory diseases, lipopolysaccharide-induced intestinal epithelial barrier dysfunction, acute pancreatitis, and steatohepatitis. TMEM16A also plays multiple roles in inflammatory processes by increasing vascular permeability and leukocyte adhesion, promoting inflammatory cytokine release, and sensing inflammation-induced pain. Furthermore, TMEM16A plays its diverse pathological roles in different inflammatory diseases depending on the disease severity, proliferating status of the cells, and its interacting partners. We herein propose cellular environment-dependent mechanisms that explain the diverse roles of TMEM16A in inflammation.
Asunto(s)
Pancreatitis , Enfermedad Aguda , Humanos , Inflamación , Lipopolisacáridos , Transducción de SeñalRESUMEN
BACKGROUND: Homeobox A9 (HOXA9), a member of the HOX protein family, plays diverse biological roles in embryonic development and carcinogenesis. The prognostic value of HOXA9 expression in nasopharyngeal carcinoma (NPC) is not well-defined. The present study aimed to analyse NPC tissue HOXA9 expression and determine prognostic significance by investigating the relationship between HOXA9 expression and clinicopathologic features. METHODS: Between January 2010 and December 2014, 252 NPC patients and 30 chronic nasopharyngitis patients (control group) were recruited to participate in the present study. Correlations between HOXA9 expression level and clinicopathologic features (including survival) were analysed. RESULTS: High HOXA9 expression was significantly associated with clinical stage (p < 0.01) and higher T stage (p < 0.01). In univariate analysis, high HOXA9 expression predicted overall survival (OS) (p = 0.011). In multivariate analysis, HOXA9 over-expression independently and significantly predicted poorer PFS (p < 0.01, hazard ratio (HR) = 2.387, 95% CI [0.876, 6.545]) and OS (p < 0.01, HR = 2.486, 95% CI [1.041, 8.926]). CONCLUSION: High HOXA9 expression is an independent prognostic factor associated with advanced tumour stage and poorer survival in NPC patients.
RESUMEN
PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory disease. The underlying epigenetic mechanisms and treatment of CRSwNP are partially understood. Of the different epigenetic changes in CRSwNP, histone deacetylases (HDACs), methylation of DNA, and the levels of miRNA are widely studied. Here, we review the human studies of epigenetic mechanisms in CRSwNP. RECENT FINDINGS: The promoters of COL18A1, PTGES, PLAT, and TSLP genes are hypermethylated in CRSwNP compared with those of controls, while the promoters of PGDS, ALOX5AP, LTB4R, IL-8, and FZD5 genes are hypomethylated in CRSwNP. Promoter hypermethylation suppresses the gene expression, while promoter hypomethylation increases the gene expression. Studies have shown the elevation in the levels of HDAC2, HDAC4, and H3K4me3 in CRSwNP. In CRSwNP patients, there is also an upregulation of certain miRNAs including miR-125b, miR-155, miR-19a, miR-142-3p, and miR-21 and downregulation of miR-4492. Epigenetics takes part in the immunology of CRSwNP and may give rise to endotypes of CRSwNP. Both HDAC2 and the miRNA including miR-18a, miR-124a, and miR-142-3p may take function in the regulation of glucocorticoid resistance. HDAC inhibitors and KDM2B have shown effectiveness in decreasing nasal polyp, and DNA methyltransferase (DNMT) or HDAC inhibitors may have a potential efficacy for the treatment of CRSwNP. Recent advances in the epigenetics of CRSwNP have led to the identification of several potential therapeutic targets for this disease. The use of epigenetics may provide novel and effective biomarkers and therapies for the treatment of nasal polyp.
Asunto(s)
Epigénesis Genética/genética , Pólipos Nasales/genética , Sinusitis/genética , Enfermedad Crónica , Femenino , Humanos , MasculinoRESUMEN
A couple of cysts lying in the pterygopalatine fossa are rare. The authors report a case of a 28-year-old woman who was admitted to the authors' hospital with a 1-month history of headache and numbness on the left head. Three-dimensional computed tomography revealed a large soft mass in the pterygopalatine fossa. Magnetic resonance imaging showed that there were a couple of cysts in the pterygopalatine fossa. One cyst measured 41â×â38â×â34âmm and the other 23â×â19â×â19âmm. A transpterygoid transnasal endoscopic approach and resection of the lesion was performed. The authors opened the cyst with coblation and the lesion showed a lot of transparent thick yellow liquid. The authors located the posterior wall the other cyst with ENT image navigation. The puncture was conducted and a lot of yellow liquid flowed out of the lesion. The patient recovered rapidly. The headache and numbness were alleviated and disappeared after 1 month. The patient currently has no evidence of recurrence at 1 year postoperatively. The coblation and ENT image navigation make the surgeon more easily to achieve risk-free surgery under endoscopy.
Asunto(s)
Quistes/cirugía , Fosa Pterigopalatina/cirugía , Adulto , Quistes/diagnóstico por imagen , Endoscopía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética , Imagen Multimodal , Fosa Pterigopalatina/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
It remains unclear that which kind of carbon support is better for improving the reactivity of nanoscale zerovalent iron (nZVI) without the adsorption effects of carbon. Finding appropriate contaminants that could be degraded by nZVI with high capacity and electron utilization is crucial for exploring the applications of nZVI. High degradation rate (up to 3.70â¯min-1) and high capacity (up to 3000â¯mgâ¯g-1) of antibiotic chloramphenicol (C11H12Cl2N2O5, CAP) removal with high electron utilization (>97%) was achieved by different carbon supported nZVI in this study. Carbon powder (CP) was found to be the best support, possessing good distribution and reactivity of nZVI. 99% of CAP was removed by CP-nZVI after 3â¯min, without the electron consumption via the side reaction between nZVI and water, suggesting that CAP could outcompete with water for the electrons from nZVI. The entire pathway of CAP removal was elucidated based on UPLC-MS/MS analysis. Partial degradation of CAP (denitration and dechlorination) was enough to take away the antimicrobial properties. These results suggest a promising application scenario of carbon supported nZVI for the remediation of CAP-contaminated water to reduce the antibiotic selection pressure of the environment.
Asunto(s)
Antibacterianos/química , Carbono/química , Cloranfenicol/química , Hierro/química , Nanopartículas/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , AdsorciónRESUMEN
Sulfidized nanoscale zerovalent iron (SNZVI) has desirable properties for in situ groundwater remediation. However, there is limited understanding of how the sulfidation type and particle properties affect the reactivity and selectivity of SNZVI toward groundwater contaminants, or how reactivity changes as the particles age. Here, SNZVI synthesized by either a one-step (SNZVI-1) or two-step (SNZVI-2) process were characterized, and the reactivity of both fresh and aged (1d to 60 d) nanoparticles was assessed. The measured S/Fe ratio was 5.4 ± 0.5 mol % for SNZVI-1 and 0.8 ± 0.1 mol % for SNZVI-2. XPS analysis indicates S2-, S22-, and S n2- species on the surface of both SNZVI-1 and SNZVI-2, while S22- is the dominant species inside of the SNZVI nanoparticles. SNZVI-1 particles were hydrophobic (contact angle = 103 ± 3°), while the other materials were hydrophilic (contact angles were 18 ± 2° and 36 ± 3° for NZVI and SNZVI-2, respectively). SNZVI-1, with greater S content and hydrophobicity, was less reactive with water than either NZVI or SNZVI-2 over a 60 d period, resulting in less H2 evolution. It also had the highest reactivity with TCE and the lowest reactivity with nitrate, consistent with its higher hydrophobicity. In contrast, both NZVI and SNZVI-2 were reactive with both TCE and nitrate. Both types of SNZVI remained more reactive after aging in water over 60 d than NZVI. These data suggest that the properties of the SNZVI made from a one-step synthesis procedure may provide better reactivity, selectivity, and longevity than that made from a two-step process.
Asunto(s)
Agua Subterránea , Tricloroetileno , Contaminantes Químicos del Agua , Hierro , AguaRESUMEN
Nasopharyngeal cancer is a type of malignant tumor with a high rate of incidence. Cancer stem cells are regarded as one of the main causes for the formation and recurrence of nasopharyngeal cancer. CXC chemokine receptor type 4 (CXCR4) has been reported to perform an important role in cancer; however, the association between CXCR4 and nasopharyngeal cancer stem cells remains unclear. The present study explored the effect of CXCR4 on cellular viability, apoptosis and invasion of nasopharyngeal cancer stem cells. Results of the present study demonstrated that knockdown of CXCR4 inhibited the viability and invasion of nasopharyngeal cancer stem cells and promoted cellular apoptosis. Further studies have revealed that the anti-tumor effect of CXCR4 knockdown was associated with the inhibition of the protein kinase B signal. These results demonstrate that the knockdown of CXCR4 resulted in an anti-tumor effect in nasopharyngeal cancer stem cells. Therefore, CXCR4 may become a promising therapeutic target in the treatment of nasopharyngeal cancer.
RESUMEN
The chlorination of azo compounds can produce halonitromethanes (HNMs), which have attracted increasing concern due to their high genotoxicity. By impacting the speciation of chlorine and azo compounds, pH impacts apparent second-order rate constants of Methyl Orange (MO, 27.5-1.4 × 103 M-1 s-1), Acid Orange II (AO, 16.7-99.3 M-1 s-1), and Acid Red 1 (AR 1, 3.7-72.5 M-1 s-1) (pH range 6.3-9.0). The two-compartment first-order model successfully described the chloropicrin (TCNM) formation kinetics, suggesting that both fast- and slow-reacting precursors of TCNM are generated from the chlorination of azo compounds. The ratios between fast and slow formation rate constants for MO and AO were 15.6-5.4 × 102, while that of AR 1 was 9.8-19.4 (pH range 6.5-9.0). The fraction of the fast-reacting TCNM precursors decreased with increasing pH for MO and AO; while that for AR 1 decreased when pH increased from 6.5 to 8.0, and then increased when pH increased from 8.0 to 9.0. The impact of pH on TCNM formation was also precursor-specific. The highest molar yields of TCNM predicted from the model in this study were 2.4%, 2.5%, and 1.5% for MO, AO, and AR 1, respectively. The study demonstrates that azo compounds are important HNM precursors, and pose a potential threat to drinking water safety.
Asunto(s)
Compuestos Azo/química , Cloro/química , Hidrocarburos Clorados/metabolismo , Naftalenos/química , Halogenación , Hidrocarburos Clorados/química , Cinética , Purificación del AguaRESUMEN
Nin one binding protein (NOB1) plays important roles in the synthesis and degradation of proteins, thus having effects on the cellular process. In the present study, the expression level of NOB1 in laryngeal cancer patients was detected by quantitative PCR and western blotting, and the effect of NOB1 on growth and metastasis of laryngeal cancer cells was explored. Silence of NOB1 was found to inhibit the proliferation of laryngeal cancer cells, arrest cell cycle and induce cell apoptosis. NOB1 silence was also found to inhibit the migration and invasion of laryngeal cancer cells and to downregulate the protein levels of matrix metalloproteinases (MMPs)-2 and MMP-9. Further mechanism study revealed that the JNK signaling pathway was involved in the function of NOB1. Our present results suggest that NOB1 plays an oncogenic role in laryngeal cancer cells through the regulation of JNK signaling pathway, and lays a theoretical foundation for further exploration of NOB1.
Asunto(s)
Proteínas Quinasas JNK Activadas por Mitógenos/fisiología , Neoplasias Laríngeas/patología , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas Nucleares/fisiología , Proteínas de Unión al ARN/fisiología , Apoptosis , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteínas Nucleares/análisis , Proteínas Nucleares/antagonistas & inhibidores , Proteínas de Unión al ARN/análisis , Proteínas de Unión al ARN/antagonistas & inhibidoresRESUMEN
F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box protein family that regulates cell cycle progression and cell growth and differentiation. FBW7 also functions as a tumor suppressor. A cisplatin (CDDP)-based multidrug chemotherapy regimen is standard for nasopharyngeal carcinoma (NPC), but drug resistance is an increasing problem. Here, we evaluated the relationship between FBW7 and multidrug resistance-associated protein (MRP), and its correlation with drug resistance in NPC, and explored the mechanism underlying drug resistance to CDDP in this disease. We used cell viability assays, Western blotting, and small interfering RNA (siRNA) interference to investigate the underlying mechanism underlying CDDP resistance in a NPC cell line. The expression of FBW7 and MRP was detected by Western blotting after siRNA interference in the CDDP-resistant NPC cell line, CNE2-CDDP. The 3-(4 5-dimethyl-2-thiazolyl)-2 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to evaluate drug sensitivity of various types of antitumor drugs, including paclitaxel (PCX), CDDP, fluorouracil (5-FU), and vincristine (VCR). We found that siRNA-mediated upregulation of FBW7 significantly increased CDDP chemosensitivity. The IC50 values of CDDP in siRNA-FBW7-CNE2-CDDP and FBW7-CNE2-CDDP-NC cells were 2.485 ± 0.155 and 4.867 ± 0.442 µmol/mL, respectively. The IC50 values of PCX, CDDP, 5-FU, and VCR were significantly decreased in siRNA-FBW7-CNE2 than in FBW7-CNE2-NC (3.46 ± 0.14 vs. 46.21 ± 6.03 µmol/mL; 3.76 ± 0.54 vs. 39.45 ± 0.96 µmol/mL; 2.14 ± 1.67 vs. 28.76 ± 1.89 µmol/mL; 4.43 ± 0.89 vs. 87.90 ± 3.45 µmol/mL, respectively). The IC50 of CDDP was significantly less in siRNA-FBW7-CNE2-CDDP than in FBW7-CNE2-CDDP-NC. The level of FBW7 expression in CNE2 cells was correlated with CDDP chemosensitivity. siRNA-mediated upregulation of FBW7 expression downregulated the expression of MRP, significantly increasing drug sensitivity in CNE2 cells.
Asunto(s)
Proteínas de Ciclo Celular/biosíntesis , Resistencia a Antineoplásicos/genética , Proteínas F-Box/biosíntesis , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Neoplasias Nasofaríngeas/genética , Ubiquitina-Proteína Ligasas/biosíntesis , Carcinoma , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Resistencia a Múltiples Medicamentos/genética , Proteínas F-Box/genética , Proteína 7 que Contiene Repeticiones F-Box-WD , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , ARN Interferente Pequeño/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
MicroRNAs (miRNAs) are small, noncoding RNAs of endogenous origin that play an important role in tumor development. Here, we examined the role of miR-152 in supragalottic laryngeal carcinoma. The expression of miR-152 was assessed by real-time PCR in tissues from 83 patients with supragalottic laryngeal carcinoma in relation to clinicopathological parameters. Cell viability was assessed by thiazolyl blue assay in Hep-2 cells transfected with miR-152 mimics or a negative control. MiR-152 was significantly downregulated in supragalottic laryngeal carcinoma tissues (t = 12.65, p < 0.001, paired t test), and its expression was correlated with pT stage (χ(2) = 26.88, p < 0.001) and pN stage (z = -3.56, p < 0.001) in patients with supragalottic laryngeal carcinoma. MiR-152 inhibited the proliferation of Hep-2 cells. MiR-152 may serve as a novel prognostic marker in patients with supragalottic laryngeal carcinoma.
Asunto(s)
Proliferación Celular , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patología , MicroARNs/genética , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
This study aimed to investigate the expression, function, and possible mechanism of Src in the Hep-2 cell line. We used Src-specific small interfering RNA (siRNA) to inhibit the expression of Src in Hep-2 cells. RT-PCR and Western blot were applied to evaluate the expression level of Src after RNA interference, and the MTT assay and flow cytometry were used to observe the expression of PI-3 K and Akt. siRNA can downregulate the expression of Src in Hep-2 cells. Downregulation of Src decreased PI-3 K and Akt expression. We found that Src knockdown inhibits the proliferation of Hep-2 cells and the growth of laryngeal carcinoma in vivo. This study has demonstrated that Src participates in the regulation of apoptosis through the Src/PI-3 K/Akt signaling pathway in the Hep-2 cell line. Silencing of Src by siRNA is a viable approach in laryngeal carcinoma treatment.
Asunto(s)
Neoplasias Laríngeas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Transducción de Señal , Familia-src Quinasas/genética , Animales , Apoptosis/genética , Línea Celular Tumoral , Supervivencia Celular/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Immunoblotting , Inmunohistoquímica , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Ratones Desnudos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ensayos Antitumor por Modelo de Xenoinjerto , Familia-src Quinasas/metabolismoRESUMEN
A novel drug named Dasatinib is a highly potent ATP-competitive orally active dual Src/Abl kinase inhibitor with anti-proliferative activity against solid tumors and CML (chronic myeloid leukaemia) cell lines. Dasatinib has been shown to have preclinical activity against human prostate, breast, pancreatic, lung, and head and neck cancer. To determine whether Dasatinib can inhibit the growth of laryngeal squamous cell carcinoma, in the present study, we investigated the antitumor effect of Dasatinib on Hep-2 cells. Hep-2 cells were treated with different concentrations of Dasatinib for different time. Cell proliferation, cell cycle distribution, and cell apoptosis were evaluated using MTT assay, flow cytometry, and fluorescent microscopy. It was found that Dasatinib exhibited significant efficacy in growth inhibition, cell cycle arrest at G0/G1 phase, and apoptosis induction in a dose- and time-dependent manner. Measuring the modulation of regulators in the cell cycle, apoptosis and signal transductions by western blot analysis showed that the effect of Dasatinib was due to suppression of the expression of Bax, Bcl-2, Caspase-3, and Caspase-8. Moreover, in vivo studies were performed in a nude mouse xenograft model, the new prescription (DDP + Dasatinib) was better than DDP alone in terms of therapeutic efficacy. In conclusion, the antitumor effect of Dasatinib on Hep-2 cells was due to the induction of cell cycle arrest as well as apoptosis. The possible mechanisms underlying the action might be attributed to the suppression of Src phosphorylation. This investigation suggests a potential clinical application of Dasatinib for the treatment of laryngeal cancer patients.
Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/patología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Laríngeas/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Tiazoles/uso terapéutico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Western Blotting , Línea Celular Tumoral , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/patología , Cisplatino/farmacología , Dasatinib , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Humanos , Técnicas In Vitro , Masculino , Ratones , Ratones Desnudos , Trasplante de Neoplasias , RatasRESUMEN
BACKGROUND: Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear. PRINCIPAL FINDINGS: Here, we show that a novel oncogenic candidate, suprabasin (SBSN), plays important roles in maintaining the anchorage-independent and anchorage-dependent cell proliferation in ACC by using SBSN shRNA stably transfected ACC cell line clones. SBSN is also important in maintaining the invasive/metastatic capability in ACC by Matrigel invasion assay. More interestingly, SBSN transcription is significantly upregulated by DNA demethylation induced by 5-aza-2'-deoxycytidine plus trichostatin A treatment and the DNA methylation levels of the SBSN CpG island located in the second intron were validated to be significantly hypomethylated in primary ACC samples versus normal salivary gland tissues. CONCLUSIONS/SIGNIFICANCE: Taken together, these results support SBSN as novel oncogene candidate in ACC, and the methylation changes could be a promising biomarker for ACC.