Lo, H.-C.H.-C.LoHsu, J.-H.J.-H.HsuLiang-Chuan LaiTsai, M.-H.M.-H.TsaiERIC YAO-YU CHUANGMONG-HSUN TSAI2021-03-082021-03-0820202045-2322https://www.scopus.com/inward/record.uri?eid=2-s2.0-85090124280&doi=10.1038%2fs41598-020-71128-1&partnerID=40&md5=47a70631a98bbd80c67b2dc561e9cc1ahttps://scholars.lib.ntu.edu.tw/handle/123456789/550999Prostate cancer is the second leading cause of cancer-related death worldwide. Radiotherapy is often applied for the treatment, but radioresistance is a challenge in some patients. MicroRNAs have been reported to be involved in the DNA damage response induced by ionizing radiation and recent studies have reported microRNA-mediated radiosensitivity. In the present study, we found microRNA-107 (miR-107) enhanced radiosensitivity by regulating granulin (GRN) in prostate cancer (PC-3) cells. MiR-107 was downregulated and GRN was upregulated in response to ionizing radiation in PC-3 cells. Overexpression of miR-107 and knockdown of GRN promoted the sensitivity of PC3 cells to ionizing radiation. By rescue experiments of GRN, we revealed that radiosensitivity enhanced by miR-107 can be attenuated by GRN overexpression in PC-3 cells. Furthermore, we showed miR-107 enhanced radiation-induced G1/S phase arrest and G2/M phase transit, and identify delayed apoptosis by suppressing p21 and phosphorylation of CHK2. Collectively, these results highlight an unrecognized mechanism of miR-107-mediated GRN regulation in response to ionizing radiation and may advance therapeutic strategies for the treatment of prostate cancer. ? 2020, The Author(s).[SDGs]SDG3GRN protein, human; microRNA; MIRN107 microRNA, human; tumor marker; apoptosis; cell proliferation; gene expression regulation; genetics; human; ionizing radiation; male; metabolism; pathology; prostate tumor; radiation tolerance; tumor cell culture; Apoptosis; Biomarkers, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Progranulins; Prostatic Neoplasms; Radiation Tolerance; Radiation, Ionizing; Tumor Cells, Culturedjournal article10.1038/s41598-020-71128-1328839622-s2.0-85090124280