RESUMEN
MicroRNAs (miRNAs) are aberrantly expressed in several tumors and play important role in tumorigenesis. However, little is known about the role of miR-613 in laryngeal squamous cell carcinoma (LSCC). We determined the expression of miR-613 in a panel of 30 LSCC specimens. Compared with the adjacent normal samples, 20 cases of LSCC tissues exhibited decreased expression of miR-613. The average expression of miR-613 in LSCC tissues was lower than in normal samples. Moreover, we demonstrated that exogenous expression of miR-613 suppressed LSCC cell proliferation, invasion, and blocked G1/S phase transition. We identified that 3-phosphoinositide-dependent protein kinase-1 (PDK1) was a direct target gene of miR-613 in LSCC cell. Overexpression of miR-613 suppressed PDK1 expression in LSCC cell. Furthermore, we demonstrated that PDK1 was upregulated in LSCC tissues. MiR-613 expression was inversely correlated with the expression of PDK1 in LSCC tissues. Moreover, we showed that PDK1 was involved in the miR-613-mediated cancer suppression of LSCC cell. These results suggested that miR-613 played as a tumor suppressor gene in LSCC partly by inhibiting PDK1 expression.
Asunto(s)
Neoplasias Laríngeas/genética , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Western Blotting , Ciclo Celular/genética , Ciclo Celular/fisiología , Línea Celular Tumoral , Proliferación Celular/genética , Proliferación Celular/fisiología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/genética , Proteínas Serina-Treonina Quinasas/genética , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND The angiotensin-converting enzyme (ACE, CD143) gene plays a crucial role in the pathology of many cancers. Previous studies mostly focused on the gene polymorphism, but the other functions of ACE have rarely been reported. The purpose of this study was to investigate the expression of ACE and its biological function, as well as its prognostic value, in laryngeal cancer. MATERIAL AND METHODS The expression of ACE was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis in 106 patients with laryngeal cancer and 85 healthy people. Then the cell proliferation was estimated after the cell lines Hep-2 were transfected with pGL3-ACE and empty vector, respectively. In addition, the relationship between ACE expression and clinicopathologic characteristics was analyzed. Finally, Kaplan-Meier analysis was used to evaluate the overall survival of patients with different ACE expression, while Cox regression analysis was conducted to reveal the prognostic value of ACE in laryngeal cancer. RESULTS Our results demonstrate that ACE is over-expressed in laryngeal cancer and thus promotes cell proliferation. The up-regulation of ACE was significantly influenced by tumor stage and lymph node metastasis. Patients with high ACE expression had a shorter overall survival compared with those with low ACE expression according to Kaplan-Meier analysis. The ACE gene was also found to be an important factor in the prognosis of laryngeal cancer. CONCLUSIONS Our study shows that the ACE gene was up-regulated, which promoted the cell proliferation, and it could be an independent prognostic marker in laryngeal cancer.
Asunto(s)
Neoplasias Laríngeas/enzimología , Peptidil-Dipeptidasa A/biosíntesis , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Neoplasias de Cabeza y Cuello/enzimología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/genética , Pronóstico , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Regulación hacia ArribaRESUMEN
Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck cancer with high mortality and incidence. MicroRNAs (miRNAs) are short, non-coding and endogenous RNAs that posttranscriptionally inhibit gene expression. In this study, we showed that miR-300 expression was downregulated in LSCC tissues compared with adjacent no-tumor tissues. MiR-300 overexpression inhibited Hep-2 cell proliferation, as well as the expression of ki-67 and PCNA. Moreover, overexpression of miR-300 repressed the cell invasion in Hep-2 cells. We identified c-ros oncogene 1 receptor tyrosine kinase (ROS1) as a direct target gene of miR-300 in Hep-2 cell. Furthermore, ROS1 expression was upregulated in LSCC tissues compared with adjacent no-tumor tissues. Interesting, there were an inverse correlation between ROS1 and miR-300 expression in the LSCC tissues. Overexpression of ROS1 increased the Hep-2 cells proliferation and invasion. Overexpression of ROS1 abrogated miR-300 induced cell growth and invasion inhibition. Therefore, our data suggested that miR-300 acted as a tumor suppressive gene in LSCC.