文献类型：期刊文献

英文题名：miR-300 regulates cellular radiosensitivity through targeting p53 and apaf1 in human lung cancer cells

作者：He, Jinpeng[1,2];Feng, Xiu[1,2,3];Hua, Junrui[1,2];Wei, Li[4,5];Lu, Zhiwei[6];Wei, Wenjun[1,2,7];Cai, Hui[4,5];Wang, Bing[1,2,7];Shi, Wengui[1,2,7];Ding, Nan[1,2];Li, He[1,2,7];Zhang, Yanan[1,2];Wang, Jufang[1,2]

第一作者：He, Jinpeng

通信作者：Wang, JF[1]

机构：[1]Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou, Gansu, Peoples R China;[2]Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Gansu, Peoples R China;[3]Lanzhou Univ, Sch Pharm, Lanzhou, Gansu, Peoples R China;[4]Gansu Prov Hosp, Clin Lab, Lanzhou, Gansu, Peoples R China;[5]Gansu Prov Hosp, Gen Surg Dept, Lanzhou, Gansu, Peoples R China;[6]Gansu Univ Chinese Med, Major Dis Prevent & Control Mol Med & Tradit Chin, Lanzhou, Gansu, Peoples R China;[7]Univ Chinese Acad Sci, Beijing, Peoples R China

第一机构：Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Chinese Acad Sci, Inst Modern Phys, 509 Nanchang Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2017

卷号：16

期号：20

起止页码：1943

外文期刊名：CELL CYCLE

收录：;Scopus(收录号：2-s2.0-85029413026);WOS:【SCI-EXPANDED(收录号:WOS:000414094300015)】；

基金：This work was supported by the National Nature Science Foundation of China (NO. 11405232, 31270895 and 31400723), the Science and Technology Research Project of Gansu Province (NO. 145RTSA012) and the Natural Science Foundation of Gansu Province (NO. 145RJZA117).

语种：英文

外文关键词：apoptosis; ionizing radiation; lung cancer; miR-300; senescence

摘要：microRNAs (miRNAs) play a crucial role in mediation of the cellular sensitivity to ionizing radiation (IR). Previous studies revealed that miR-300 was involved in the cellular response to IR or chemotherapy drug. However, whether miR-300 could regulate the DNA damage responses induced by extrinsic genotoxic stress in human lung cancer and the underlying mechanism remain unknown. In this study, the expression of miR-300 was examined in lung cancer cells treated with IR, and the effects of miR-300 on DNA damage repair, cell cycle arrest, apoptosis and senescence induced by IR were investigated. It was found that IR induced upregulation of endogenous miR-300, and ectopic expression of miR-300 by transfected with miR-300 mimics not only greatly enhanced the cellular DNA damage repair ability but also substantially abrogated the G2 cell cycle arrest and apoptosis induced by IR. Bioinformatic analysis predicted that p53 and apaf1 were potential targets of miR-300, and the luciferase reporter assay showed that miR-300 significantly suppressed the luciferase activity through binding to the 3-UTR of p53 or apaf1 mRNA. In addition, overexpression of miR-300 significantly reduced p53/apaf1 and/or IR-induced p53/apaf1 protein expression levels. Flow cytomertry analysis and colony formation assay showed that miR-300 desensitized lung cancer cells to IR by suppressing p53-dependent G2 cell cycle arrest, apoptosis and senescence. These data demonstrate that miR-300 regulates the cellular sensitivity to IR through targeting p53 and apaf1 in lung cancer cells.