机构：[1]Laboraotary of Radiation Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.[2]State Key Lab of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.[3]Qingdao Municipal Center for Disease Control and Prevention of Qingdao, Qingdao, Institute of Preventive Medicine, Qingdao, Shandong, China.[4]Laboraotary of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.[5]Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China.[6]NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, China.
Keloids are benign dermal tumors that arise from abnormal wound healing processes following skin lesions. Surgical excision followed by radiotherapy plays an important role in the treatment of keloids. Nevertheless, radioresistance remains a serious impediment to treatment efficacy. Investigation of the molecular response of keloids to radiation may contribute to radiosensitizing strategies.Primary keloid fibroblasts from human keloids were isolated and irradiated with X-ray. The expression profiles of messenger RNA (mRNA) in nonradiated and irradiated primary keloid fibroblasts were measured by mRNA sequencing analysis. Then, we identified common motifs and corresponding transcription factors of dysregulated mRNAs by using bioinformatic analysis of the proximal promoters. Whereafter, GO and KEGG were used to analyze the functional enrichment of the differentially expressed genes.We found that radiation not only suppressed proliferation but also increased cell senescence of primary keloid fibroblasts. There were 184 mRNAs and 204 mRNAs that showed significant changes in 4 and 8 Gy irradiated primary keloid fibroblasts, respectively. Among them, 8 upregulated and 30 downregulated mRNAs showed consistent alterations in 4 and 8 Gy irradiated primary keloid fibroblasts. More importantly, the xForkhead box O1 (FOXO1) signaling pathway was involved in the irradiation response. Pretreatment with the FOXO1 signaling inhibitor AS1842856 significantly promoted LDH release, apoptosis and senescence of primary keloid fibroblasts following irradiation.Our findings illustrated the molecular changes in human keloid fibroblasts in response to radiation, and FOXO1 pathway inhibition is expected to provide a novel strategy for the radiosensitization of keloids.
基金：
National Natural Science Foundation
of China under Grant [number 82073477 and 32071238]; Excellent
Youth Project of Sichuan Province; Central Funds for Sichuan
Province [number 2021ZYD0073] and the Young Talent Project of
China National Nuclear Corporation.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|3 区医学
小类|2 区核科学技术3 区生物学3 区核医学
最新[2023]版：
大类|4 区医学
小类|3 区生物学3 区核科学技术4 区核医学
第一作者：
第一作者机构：[1]Laboraotary of Radiation Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.[2]State Key Lab of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.[3]Qingdao Municipal Center for Disease Control and Prevention of Qingdao, Qingdao, Institute of Preventive Medicine, Qingdao, Shandong, China.
共同第一作者：
通讯作者：
通讯机构：[1]Laboraotary of Radiation Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.[4]Laboraotary of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.[5]Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China.[6]NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, China.[*1]Department of Plastic and Burn Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China[*2]No.17,Section 3,South People’s Rd, West China Second University Hospital, Sichuan University, Chengdu 610041, China
推荐引用方式(GB/T 7714)：
Hong Min,Li Xiaoqian,Liu Yulan,et al.Molecular response of keloids to ionizing radiation: targeting FOXO1 radiosensitizes keloids[J].International journal of radiation biology.2022,1-10.doi:10.1080/09553002.2022.2121871.
APA：
Hong Min,Li Xiaoqian,Liu Yulan,Mo Wei,Shi Bin...&Zhang Shuyu.(2022).Molecular response of keloids to ionizing radiation: targeting FOXO1 radiosensitizes keloids.International journal of radiation biology,,
MLA：
Hong Min,et al."Molecular response of keloids to ionizing radiation: targeting FOXO1 radiosensitizes keloids".International journal of radiation biology .(2022):1-10
