RESUMEN
MicroRNAs are critical regulators of the development and progression of laryngeal squamous cell carcinoma (LSCC). However, the role of microRNA-154 (miR-154) in the development and progression of LSCC has not been clarified. We found that down-regulated miR-154 expression in LSCC tissues was associated with poorer prognosis in LSCC patients. MiR-154 over-expression inhibited the proliferation, clonogenicity, and migration of LSCC cells and induced cell cycle arrest, which were reversed by miR-154 inhibition. MiR-154 targeted GALNT7 expression by reducing GALNT7-regulated luciferase activity in LSCC cells while up-regulating GALNT7 mRNA transcription in LSCC tissues and cells. GALNT7 silencing significantly attenuated the proliferation, clonogenicity, and migration of LSCC cells and induced cell cycle arrest. Finally, intravenous treatment with lentivirus for miR-154, but not scrambled control miRNA, significantly restrained the growth of implanted LSCC Hep-2 tumors and decreased the tumor mass by reducing GALNT7 expression in mice. Therefore, miR-154 may serve as a novel prognostic marker and therapeutic target for LSCC.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patología , MicroARNs/genética , N-Acetilgalactosaminiltransferasas/deficiencia , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Puntos de Control del Ciclo Celular , Movimiento Celular , Proliferación Celular , Células Cultivadas , Femenino , Humanos , Neoplasias Laríngeas/metabolismo , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , N-Acetilgalactosaminiltransferasas/genética , N-Acetilgalactosaminiltransferasas/metabolismo , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/genética , ARN Mensajero/metabolismo , Polipéptido N-AcetilgalactosaminiltransferasaRESUMEN
OBJECTIVES: To quantitatively analyze the vibratory characteristics of vocal folds before and after conservative treatments to evaluate the outcomes of conservative treatments for vocal fold leukoplakia using videostrobokymography (VSK). STUDY DESIGN: This is a prospective study. METHODS: Twenty patients and 20 controls were enrolled into the study. All patients received conservative treatments for 3 weeks and received VSK examination before and 3 weeks after the treatments. All controls only received VSK examination once. Vocal fold lengths of 25%, 50%, and 75% were chosen as the line-scan positions to evaluate the vocal fold vibration. Open quotient (OQ) and asymmetry index (AI) were obtained using VSK. RESULTS: Significant improvements in the main symptoms including voice hoarseness were found. Videostroboscopic findings showed that the white lesions on the vocal folds almost completely disappeared in all patients, and the vocal fold flexibility returned to normal. All OQs and AIs at each line-scan position in patients before the treatments were larger than those in controls (P < 0.017), whereas all OQs and AIs at each line-scan position decreased 3 weeks after conservative treatments (P < 0.017). No significant differences in OQs and AIs at each line-scan position were detected between patients after the treatments and controls (P > 0.017). CONCLUSIONS: VSK could quantitatively evaluate the vibratory characteristics of vocal folds before and after the treatments, and conservative treatment could improve VSK measurements to normal control values, suggesting that VSK is a tool to assess the outcomes of the conservative treatments for vocal fold leukoplakia.