title: Vitamin D3 up-regulated protein 1(VDUP1) is regulated by FOXO3A and miR-17-5p at the transcriptional and post-transcriptional levels, respectively, in senescent fibroblasts.
abstract: Vitamin D(3) up-regulated protein 1 (VDUP1) plays multifunctional roles in diverse cellular responses, particularly in its relation to proliferation, apoptosis, differentiation, and diseases such as cancer and stress-related diseases. In this study, we demonstrated that VDUP1 was up-regulated during the senescence process. Our results showed that overexpression of VDUP1 in young cells caused typical signs of senescence. We also found that VDUP1 knockdown delayed the onset of Ras-induced cellular senescence. Subsequently, we found that FOXO3A, whose activity increased in senescent cells, transcriptionally up-regulates VDUP1 expression and miR-17-5p, whose expression decreased in senescent cells, directly interacted with the 3'-untranslated region of VDUP1 transcripts, and destabilized VDUP1 mRNA in young cells. These results indicated that VDUP1 expression was regulated by FOXO3A at the transcriptional level and by miR-17-5p at the post-transcriptional levels during the senescence process.
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 100191 Beijing, China.
authors.forename: De Xiang
authors.initials: de X
authors.lastname: Zhuo
authors.forename: Xiao Hua
authors.initials: XH
authors.lastname: Niu
authors.forename: Yi Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Dian Qi
authors.initials: DQ
authors.lastname: Xin
authors.forename: Ying Lu
authors.initials: YL
authors.lastname: Guo
authors.forename: Ze Bin
authors.initials: ZB
authors.lastname: Mao
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D005347:Fibroblasts; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; C486715:TXNIP protein, human; D018631:ras Proteins