RESUMEN
Previous study has demonstrated that high mobility group nucleosome-binding domain 5 (HMGN5) is involved in tumorigenesis and the development of multidrug resistance in several human cancers. However, the role of HMGN5 in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we showed that HMGN5 was significantly upregulated in ESCC cells. Knockdown of HMGN5 significantly inhibited cell growth and induced cell apoptosis of ESCC cells. Moreover, knockdown of HMGN5 increased the sensitivity of ESCC cells towards cisplatin. By contrast, overexpression of HMGN5 showed the opposite effects. Further experiments demonstrated that HMGN5 regulated the expression of multidrug resistance 1, cyclin B1, and Bcl-2. Overall, our results reveal that HMGN5 promotes tumor progression of ESCC and is also an important regulator of chemoresistance. Our study suggests that inhibition of HMGN5 may be a potential strategy for improving effectiveness of ESCC treatment.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Escamosas/metabolismo , Cisplatino/farmacología , Neoplasias Esofágicas/metabolismo , Proteínas HMGN/genética , Transactivadores/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Apoptosis , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Proteínas HMGN/metabolismo , Humanos , Interferencia de ARN , ARN Interferente Pequeño/genética , Transactivadores/metabolismoRESUMEN
A growing body of evidence suggests that frizzled-7 (FZD7) is an important oncogene in multiple human malignancies and is involved in regulating sensitivity to chemotherapeutic drugs. However, little is known about the expression and function of FZD7 in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the functional significance of FZD7 in ESCC. Here, we found that both mRNA and protein expression levels of FZD7 were highly upregulated in ESCC cell lines. The knockdown of FZD7 inhibited cell growth, induced cell apoptosis, and suppressed cell migration and invasion of ESCC cells in vitro. Furthermore, knockdown of FZD7 promoted chemosensitivity to cisplatin in ESCC cells and suppressed the expression of multidrug resistance protein 1. Moreover, the silencing of FZD7 also significantly impeded the activation of Wnt signaling in ESCC cells. Taken together, our study reveals an oncogenic role of FZD7 in the progression of ESCC and suggests that FZD7 might serve as a potential therapeutic target for treatment of ESCC.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Cisplatino/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Esófago/efectos de los fármacos , Receptores Frizzled/genética , Vía de Señalización Wnt , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Esófago/metabolismo , Esófago/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Interferencia de ARN , ARN Interferente Pequeño/genética , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
14-3-3 proteins are a family of highly conserved acidic proteins that regulate cellular processes. They act as a kind of important signaling molecules taking part in many crucial decisions throughout the development process. We have isolated and characterized two members of the 14-3-3 family, namely, Dj14-3-3 α and Dj14-3-3 ζ in the planarian Dugesia japonica. The Dj14-3-3 α and ζ genes encode polypeptides of 260 and 255 amino acids respectively. We have proved that the Dj14-3-3 α and ζ genes were especially expressed in the pharynx in adult and regenerating planarians by in situ hybridization and they were not involved in regeneration process. Besides, Dj14-3-3 α and ζ genes can compensate each other in planarians by RNA interference. The Dj14-3-3 α and ζ were significantly up-regulated expression when planarians were stimulated with the pathogen-associated molecular patterns including lipopolysaccharide (LPS), peptidoglycan (PGN), ß-Glu and Poly (I:C), indicating that the Dj14-3-3 α and ζ may be involved in the immune responses.
Asunto(s)
Proteínas 14-3-3/genética , Proteínas del Helminto/genética , Planarias/genética , Planarias/inmunología , Proteínas 14-3-3/inmunología , Animales , Regulación de la Expresión Génica , Proteínas del Helminto/inmunología , Moléculas de Patrón Molecular Asociado a Patógenos/farmacología , Faringe/fisiología , Planarias/fisiología , Interferencia de ARN , Regeneración/genéticaRESUMEN
Puromycin-sensitive aminopeptidase (PSA) belongs to the M1 zinc metallopeptidase family. PSA is the most abundant aminopeptidase in the brain and plays a role in the metabolism of neuropeptides including those involved in neurodegeneration. A cDNA DjPsa was identified from the planarian Dugesia japonica cDNA library. It contains a 639-bp open reading frame corresponding to a deduced protein of 212 amino acids. Whole mount in situ hybridization revealed that DjPsa is expressed in the brain and ventral nerve cords of intact and regenerating animals and demonstrates a tissue and stage-specific expression pattern of DjPsa in developing embryos and larvae. Knocking down DjPsa gene expression with RNA interference during planarian regeneration inhibits the brain reformation completely. The results suggest that DjPsa is required for planarian brain regeneration.