机构：[1]Center for Research on Reproduction and Women’s Health, University of Pennsylvania, Philadelphia, PA 19104, USA[2]Department of Gynecology and Obstetrics, Key Laboratoryof Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, P.R. China[3]KeyLaboratory for Stem Cells and Tissue Engineering, Ministry of Education, Center for Stem Cell Biology and Tissue Engineering, Department of Biology, Zhongshan School ofMedicine, Sun Yat-Sen University, Guangzhou 510080, P.R. China[4]Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China首都医科大学附属北京友谊医院[5]Obstetrics and GynecologyHospital of Fudan University, Shanghai 200011, P.R. China[6]Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA[7]Department ofPathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA[8]Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA19104, USA[9]Shanghai Respiratory Research Institute, Shanghai 200032, P. R. China[10]Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, FudanUniversity, Shanghai 200032, P. R. China[11]Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China
LIN28B is an evolutionarily conserved RNA-binding protein that regulates mRNA translation and miRNA let-7 maturation in embryonic stem cells and developing tissues. Increasing evidence demonstrates that LIN28B is activated in cancer and serves as a critical oncogene. However, the underlying molecular mechanisms of LIN28B function in tumorigenesis are still largely unknown. Here we report that LIN28B was expressed in over half of the patients with epithelial ovarian cancer who were examined (n = 584). Functional experiments demonstrated that LIN28B inhibited ovarian cancer cell apoptosis. Furthermore, we showed that the proapoptotic factor BIM played an essential role in the antiapoptotic function of LIN28B. RNA-IP microarray analysis suggested that LIN28B binds to mRNAs that are associated with the DNA damage pathway, such as AKT2, in ovarian cancer cells. By binding to AKT2 mRNA and enhancing its protein expression, LIN28B regulated FOXO3A protein phosphorylation and decreased the transcriptional level of BIM, which antagonized the antiapoptosis activity of LIN28B. Taken together, these results mechanistically linked LIN28B and the AKT2/FOXO3A/BIM axis to the apoptosis pathway. The findings may have important implications in the diagnosis and therapeutics of ovarian cancer.
基金：
This work was supported, in whole or in part,
by grants from The Science and Technology R&D Program of Chengdu (2015-HM01-
00018-SF to X.L.), the Applied Basic Research Programs of Science and Technology
Department Foundation of Sichuan Province (2016JY0122 to X.L.), the Key Research
Projects of Science and Technology Department Foundation of Sichuan Province
(2017SZ0141 to X.L.), the National Key R&D Program of China (2017YFA0105501 to X.Z.),
Guangdong Province Science and Technology Project (2015A020212019 to X.Z.), the
Basser Center for BRCA (L.Z.), the Harry Fields Professorship (L.Z.), the US National
Institutes of Health (R01CA142776 to L.Z., R01CA190415 to L.Z., R01CA148759 to Q.H.,
and R01NS094533 to Y.F.), and the Marsha Rivkin Center for Ovarian Cancer Research
(L.Z.). X.L. was supported by the China Scholarship Council.
第一作者机构：[1]Center for Research on Reproduction and Women’s Health, University of Pennsylvania, Philadelphia, PA 19104, USA[2]Department of Gynecology and Obstetrics, Key Laboratoryof Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, P.R. China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Xiaojuan Lin,Jianfeng Shen,Dan Peng,et al.RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells.[J].SIGNAL TRANSDUCTION AND TARGETED THERAPY.2018,3:doi:10.1038/s41392-018-0026-5.
APA：
Xiaojuan Lin,Jianfeng Shen,Dan Peng,Xinhong He,Congjian Xu...&Xiaomin Zhong.(2018).RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells..SIGNAL TRANSDUCTION AND TARGETED THERAPY,3,
MLA：
Xiaojuan Lin,et al."RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells.".SIGNAL TRANSDUCTION AND TARGETED THERAPY 3.(2018)
医学