Differential miRNA expression profiling reveals miR-205-3p to be a potential radiosensitizer for low- dose ionizing radiation in DLD-1 cells

Abstract

Indexación: Scopus.Departamento de Oncología Básico-Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile 2Comisión Chilena de Energía Nuclear, Santiago, Chile 3Center for Research and Applications in Plasma Physics and Pulsed Power, P4, Chile 4Departamento de Ciencias Físicas, Universidad Andres Bello, Santiago, Chile 5Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile 6Current Address: Center of Excellence in Precision Medicine, Pfizer, Chile. on IR responsive modeling. This work was supported by Anillo grant ACT1115 and ACT172101, PIA Program, CONICYT; the Chilean doctoral fellowship 21130246Enhanced radiosensitivity at low doses of ionizing radiation (IR) (0.2 to 0.6 Gy) has been reported in several cell lines. This phenomenon, known as low doses hyperradiosensitivity (LDHRS), appears as an opportunity to decrease toxicity of radiotherapy and to enhance the effects of chemotherapy. However, the effect of low single doses IR on cell death is subtle and the mechanism underlying LDHRS has not been clearly explained, limiting the utility of LDHRS for clinical applications. To understand the mechanisms responsible for cell death induced by low-dose IR, LDHRS was evaluated in DLD-1 human colorectal cancer cells and the expression of 80 microRNAs (miRNAs) was assessed by qPCR array. Our results show that DLD-1 cells display an early DNA damage response and apoptotic cell death when exposed to 0.6 Gy. miRNA expression profiling identified 3 over-expressed (miR-205-3p, miR-1 and miR-133b) and 2 downregulated miRNAs (miR-122-5p, and miR-134-5p) upon exposure to 0.6 Gy. This miRNA profile differed from the one in cells exposed to high-dose IR (12 Gy), supporting a distinct low-dose radiation-induced cell death mechanism. Expression of a mimetic miR- 205-3p, the most overexpressed miRNA in cells exposed to 0.6 Gy, induced apoptotic cell death and, more importantly, increased LDHRS in DLD-1 cells. Thus, we propose miR-205-3p as a potential radiosensitizer to low-dose IR. © Andaur et al.http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=25405&path[]=7956