RESUMEN
p53R2 is a p53-inducible ribonucleotide reductase subunit involved in deoxyribonucleotide biosynthesis and DNA repair. Although p53R2 has been linked to human cancer, its role in cervical cancer remains unknown. In this study, we investigated the expression and clinical significance of p53R2 in early-stage cervical cancer. p53R2 expression is significantly upregulated at both mRNA and protein levels in cervical cancer cells and tissues, compared with that in matched normal cervical cells and tissues, respectively. p53R2 overexpression is associated with increased risk of pelvic lymph node metastasis (PLNM, p = 0.001) and cancer relapse (p = 0.009). Patients with high p53R2 expression have a shorter overall survival (OS) and disease-free survival (DFS). p53R2 is an independent factor for predicting OS and DFS of cervical cancer patients. We further show that p53R2 is important for oncogenic growth, migration and invasion in cervical cancer cells. Mechanistically, p53R2 promotes Akt signaling and epithelial-mesenchymal transition (EMT). In conclusion, our study demonstrates for the first time that p53R2 protein is overexpressed in early-stage cervical cancer and unravels some unconventional oncogenic functions of p53R2. p53R2 may be a useful prognostic biomarker and therapeutic target for cervical cancer.
Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ribonucleótido Reductasas/metabolismo , Transducción de Señal , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , Análisis de SupervivenciaRESUMEN
A novel multifunctional aggregation-induced emission (AIE) nanoaggregate for targeted imaging and enzyme-triggered chemotherapy was successfully fabricated via a one-step assembly. In this system, a quaternary ammonium-modified tetraphenylethene derivative (QA-TPE) acted as the AIE fluorophore as well as the chemotherapeutic agent, and a water-soluble acidic polysaccharide, hyaluronic acid (HA) acted as the aggregation-inducing scaffold, AIE turn-on agent, and targeting agent for CD44 receptor-mediated cancer cells. More importantly, HA endowed the QA-TPE/HA nanoaggregate both good biocompatibility and hysteretic chemotherapy activity, which were achieved by controlling the release of QA-TPE using the endogenous HAase in CD44 receptor-mediated cancer cells.
