Differential miRNA expression profiling reveals miR-205-3p to be a potential radiosensitizer for low- dose ionizing radiation in DLD-1 cells
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Rodrigo Andaur1, Julio C. Tapia1,5, José Moreno2,3,4, Leopoldo Soto2,3,4, Ricardo Armisen1,5,6 and Katherine Marcelain1,5
1Departamento 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, Talca, 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, Santiago, Chile
Katherine Marcelain, email: [email protected]
Keywords: radiosensitivity; low-dose ionizing radiation; miRNA; miR-205-3p
Received: June 23, 2017 Accepted: April 28, 2018 Published: May 29, 2018
Enhanced 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 hyper-radiosensitivity (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 down-regulated 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.
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