RESUMEN
To analyse the risk factors and healing factors of pharyngocutaneous fistula (PCF) in patients with laryngeal cancer after total laryngectomy, and to explore the relevant epidemiology. A retrospective analysis was conducted on laryngeal cancer patients who underwent total laryngectomy in our hospital from January 2010 to December 2022. The 349 patients included in the study were divided into a PCF group of 79 and a non-PCF group of 270. Perform one-way analysis of variance and multivariate logistic analysis on various data of patients included in the statistics, and analyse the risk factors and healing factors of PCF. Smoking, history of radiation therapy for laryngeal cancer, history of chemotherapy for laryngeal cancer, tumour location (larynx, pharynx, oesophagus), preoperative albumin, postoperative proteinaemia, <99 haemoglobin, postoperative haemoglobin, postoperative C-reactive protein (CRP) level are the risk factors for PCF. Also, radiation therapy and postoperative proteinaemia were the main reasons for preventing PCF healing. Smoking history, laryngeal cancer, radiation therapy, albumin, haemoglobin and CRP are risk factors for postoperative PCF after total laryngectomy, while radiation therapy and postoperative hypoalbuminaemia are key factors affecting PCF healing.
Asunto(s)
Fístula Cutánea , Neoplasias Laríngeas , Laringectomía , Enfermedades Faríngeas , Complicaciones Posoperatorias , Humanos , Laringectomía/efectos adversos , Neoplasias Laríngeas/cirugía , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Estudios Retrospectivos , Fístula Cutánea/etiología , Fístula Cutánea/epidemiología , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Enfermedades Faríngeas/etiología , Enfermedades Faríngeas/epidemiología , Cicatrización de Heridas , AdultoRESUMEN
Emerging evidence suggests that long non-coding RNA (lncRNA) is closely associated with numerous human diseases, including cancer. However, the functional relevance of lncRNA in human laryngeal squamous cell carcinoma (LSCC) is largely unknown. In the current study, we described CCAT2, a previously unappreciated oncogenic lncRNA in LSCC. CCAT2 was significantly upregulated in human LSCC tissue and serum samples, associated with larger tumor volume, higher clinical stage, and poorer differentiation status. Lentivirus-mediated CCAT2 knockdown notably repressed the cell viability, colony formation, and DNA synthesis rate of LSCC. Screening of transcription factors revealed that YAP/TEAD activity was affected by CCAT2 in LSCC cells. Further, CCAT2 directly binds to YAP protein and blocks the phosphorylation of YAP induced by LATS1, resulting in the nuclear translocation of YAP and the activation of YAP oncogenic targets, such as CTGF, CYR61 and AMOTL2. Importantly, we also confirmed the regulation of CCAT2 on YAP activity in vivo based on nude mice model. Altogether, we identified a novel lncRNA that controls YAP nucleocytoplasmic shuttling and promotes LSCC cell proliferation. Given the importance of YAP in tumorigenesis and progression, our results provide insights to intervene LSCC by targeting the CCAT2/YAP axis.
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patología , ARN Largo no Codificante/fisiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Animales , Carcinoma de Células Escamosas/terapia , Proliferación Celular/genética , Supervivencia Celular/genética , ADN de Neoplasias/metabolismo , Modelos Animales de Enfermedad , Humanos , Neoplasias Laríngeas/terapia , Ratones Desnudos , Terapia Molecular Dirigida , Fosforilación/genética , Unión Proteica/genética , Proteínas Serina-Treonina Quinasas/fisiología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células Tumorales Cultivadas , Regulación hacia Arriba/genéticaRESUMEN
Long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of various cancers, including laryngeal squamous cell carcinoma (LSCC). Recently, lncRNA Sox2 overlapping transcript (SOX2-OT) has been identified as an oncogene in various cancers. However, the functional role and the regulatory mechanism of SOX2-OT in LSCC remains unclear. In this study, we found that SOX2-OT expression was increased and negatively correlated with PTEN expression in LSCC tissues. Furthermore, SOX2-OT overexpression promoted LSCC cell proliferation, migration, invasion, and suppressed cell apoptosis in vitro, as well as facilitated the in vivo tumorigenicity. By contrast, SOX2-OT silencing exerted the opposite effect. Mechanically, SOX2-OT interacted with EZH2 and recruited EZH2 to induce H3K27me3 and epigenetically inhibited PTEN expression in LSCC cells. Additionally, EZH2 silencing and PTEN overexpression significantly abrogated the SOX2-OT overexpression-mediated promotion of LSCC cell malignant behavior. Collectively, our findings demonstrate that SOX2-OT inhibits PTEN expression to facilitate LSCC development through EZH2-mediated H3K27me3. © 2019 IUBMB Life, 71(9):1230-1239, 2019.
Asunto(s)
Carcinoma de Células Escamosas/genética , Proteína Potenciadora del Homólogo Zeste 2/genética , Neoplasias Laríngeas/genética , Fosfohidrolasa PTEN/genética , Animales , Apoptosis/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Epigénesis Genética/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Histona Demetilasas con Dominio de Jumonji/genética , Neoplasias Laríngeas/patología , Masculino , Ratones , ARN Largo no Codificante/genética , Trasplante HeterólogoRESUMEN
Connexin26 (Cx26, encoded by GJB2) mutations are the most common cause of non-syndromic deafness. GJB2 is thought to be involved in noise-induced hearing loss (NIHL). However, the role of Cx26 in NIHL is still obscure. To explore the association between Cx26 and NIHL, we established a Cx26 knockdown (KD) mouse model by conditional knockdown of Cx26 at postnatal day 18 (P18), and then we observed the auditory threshold and morphologic changes in these mice with or without noise exposure. The Cx26 KD mice did not exhibit substantial hearing loss and hair cell degeneration, while the Cx26 KD mice with acoustic trauma experienced higher hearing loss than simple noise exposure siblings and nearly had no recovery. Additionally, extensive outer hair cell loss and more severe destruction of the basal organ of Corti were observed in Cx26 KD mice after noise exposure. These data indicate that reduced Cx26 expression in the mature mouse cochlea may increase susceptibility to noise-induced hearing loss and facilitate the cell degeneration in the organ of Corti.