Int J Biol Sci 2019; 15(10):2240-2255. doi:10.7150/ijbs.35356
miR-27a-containing Exosomes Secreted by Irradiated Skin Keratinocytes Delayed the Migration of Unirradiated Skin Fibroblasts
1. State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province, P. R. China 215123
2. Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Institute of Radiotherapy & Oncology, Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu Province, 215004, P. R. China
Tan W, Zhang Y, Li M, Zhu X, Yang X, Wang J, Zhang S, Zhu W, Cao J, Yang H, Zhang L. miR-27a-containing Exosomes Secreted by Irradiated Skin Keratinocytes Delayed the Migration of Unirradiated Skin Fibroblasts. Int J Biol Sci 2019; 15(10):2240-2255. doi:10.7150/ijbs.35356. Available from http://www.ijbs.com/v15p2240.htm
Radiation-induced bystander effect (RIBE), e.g. the biological response occurring in unirradiated cells when their neighboring cells are irradiated, is the consequence of intercellular communication between irradiated and unirradiated cells and intracellular signal transduction of these two cell populations. Although several miRNAs have been found to play an important role in RIBEs, the evidence for the regulatory effects of miRNAs on RIBEs is still limited. In this study, by using a two cell-line co-culture system, we first found that the migration of unirradiated bystander WS1 skin fibroblasts was inhibited after co-culture with irradiated HaCaT skin keratinocytes. Further study revealed that HaCaT cells exposed to α-particles and X-rays quickly showed an elevated miR-27a expression, which was essential for the induction of the bystander effect, resulting in the secretion of miR-27a-containing exosomes as a major RIBE signaling factor. Upon uptake of these exosomes, the recipient unirradiated WS1 cells displayed oxidative stress and increased miR-27a levels. Elevated levels of miR-27a that targets MMP2 in the recipient WS1 cells then led to slowed cell migration, which was dependent upon the redox status of WS1 cells. To summarize, the present study has revealed a critical role of miR-27a in every step of the induction of bystander migration inhibition of unirradiated WS1 fibroblasts co-cultured with irradiated HaCaT keratinocytes, confirming the important regulatory effects of miRNAs in RIBEs. Additionally, we provided direct evidence that RIBEs could affect wound healing.
Keywords: radiation-induced bystander effect, intercellular communication, cell migration, miR-27a, exosomes, ROS