RESUMEN
The circular RNA ciRS-7 has been reported to be involved in the pathogenesis of various tumors, including gastric and colorectal cancer. However, the role of ciRS-7 in esophageal squamous cell carcinoma (ESCC) remains unsolved. In this study, we found that the ciRS-7 expression was significantly upregulated in ESCC cancer tissues compared with matched normal tissues and associated with poor patient survival. Overexpression of ciRS-7 abrogated the tumor-suppressive roles of miR-7 including cell proliferation, migration and invasion in vitro as well as tumor growth and lung metastasis in vivo. Mechanistically, ciRS-7 functioned as the sponge of miR-7 and reactivated its downstream HOXB13-mediated NF-κB/p65 pathway. Conclusively, our findings demonstrate how ciRS-7 induces malignant progression of ESCC and that ciRS-7 may act as a novel prognostic marker and therapeutic target for this lethal disease.
Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Proteínas de Homeodominio/metabolismo , MicroARNs/metabolismo , ARN/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Supervivencia sin Enfermedad , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidad , Femenino , Proteínas de Homeodominio/antagonistas & inhibidores , Proteínas de Homeodominio/genética , Humanos , Estimación de Kaplan-Meier , Masculino , MicroARNs/genética , Persona de Mediana Edad , Fosforilación , Pronóstico , ARN/genética , Interferencia de ARN , ARN Circular , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Factor de Transcripción ReIA/metabolismoRESUMEN
The repair activities and reaction mechanisms of phenylpropanoid glycosides (PPGs) and their analogues, isolated from Chinese folk medicinal herbs, towards oxidative DNA damage were studied with pulse radiolytic technique. On pulse irradiation of nitrogen-saturated 4 mM poly C aqueous solution containing one of the tested polyphenols, 40 mM K2S2O8 and 200 mM t-BuOH, the transient absorption spectrum of the oxidative radical of poly C decays with the concurrent formation of the phenoxyl radical of the tested polyphenols within several tens of microseconds after the electron pulse irradiation. The result indicated that there was a repair reaction between oxidative radical of poly C and the tested polyphenols. The repair activities also were observed for the tested polyphenols towards the radical cations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The rate constants were determined to be 3.7-6.4 x 10(9), 4.8-5.5 x 10(8) and 8.8-10.3 x 10(8) M(-1).sec(-1) for the repair reactions of oxidative radical of poly C and radical cations of ssDNA and dsDNA, respectively. The result of this study together with those of our previous studies demonstrates that PPGs and their analogues can fast repair not only the damage of deoxynucleoside and deoxynucleotide but also the damage of integral DNA, with the latter being closer to a cellular condition.
