title: The RNA-binding protein HuR stabilizes survivin mRNA in human oesophageal epithelial cells.
abstract: Overexpression of survivin, a member of the IAP (inhibitor of apoptosis) family, has been correlated with poorer outcomes in multiple malignancies, including oesophageal cancer. The regulatory mechanisms, particularly at the post-transcriptional level, involved in survivin overexpression are not well understood. Previous work from our group has shown that the RNA-binding protein HuR (Hu antigen R), which is also overexpressed in several malignancies, stabilizes the mRNA of XIAP (X-linked IAP), another IAP family member. In the present study, we demonstrate the binding of HuR to a 288 bp fragment in the 3'-UTR (untranslated region) of survivin mRNA in human oesophageal epithelial cells. Unexpectedly, overexpression of HuR led to a decrease in survivin expression. This was associated with decreased survivin mRNA and promoter activity, suggesting a decrease in transcription. Levels of p53, a negative transcriptional regulator of survivin, increased following HuR overexpression, in conjunction with enhanced p53 mRNA stability. Silencing p53 prior to HuR overexpression resulted in increased survivin protein and mRNA stability. These results demonstrate that, in the absence of p53, HuR overexpression results in increased survivin mRNA stability and protein expression. This provides an additional explanation for the increased survivin expression observed in oesophageal cancer cells that have lost p53.
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: James M
authors: JM
authors: Donahue
authors: Elizabeth T
authors: ET
authors: Chang
authors: Lan
authors: L
authors: Xiao
authors: Peng-Yuan
authors: PY
authors: Wang
authors: Jaladanki N
authors: JN
authors: Rao
authors: Douglas J
authors: DJ
authors: Turner
authors: Jian-Ying
authors: JY
authors: Wang
authors: Richard J
authors: RJ
authors: Battafarano
mesh_terms: D020413:3' Untranslated Regions; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004847:Epithelial Cells / Q000378:metabolism*; D004947:Esophagus / Q000166:cytology / Q000378:metabolism*; D016158:Genes, p53; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D000077022:Survivin
chemical_list: D020413:3' Untranslated Regions; D000954:Antigens, Surface; C107489:BIRC5 protein, human; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000077022:Survivin