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.
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.
Zhuo
De Xiang
de X
Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 100191 Beijing, China.
Niu
Xiao Hua
XH
Chen
Yi Cheng
YC
Xin
Dian Qi
DQ
Guo
Ying Lu
YL
Mao
Ze Bin
ZB
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
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