Stabilization of Snail by HuR in the process of hydrogen peroxide induced cell migration.
Snail functions as a key regulator in the induction of a phenotypic change called epithelial to mesenchymal transition (EMT). Aberrant expression of Snail prevails in the onset and development of tumor. Here, we have observed increased expression of Snail under the treatment of hydrogen peroxide (H(2)O(2)). Investigation into the underlying mechanisms revealed that stabilization of Snail mRNA contributes partially to this process. H(2)O(2)-induced the luciferase activity of the reporter construct contains the 3'UTR of Snail. Deletion of the AU-rich elements in the UTR eliminated the response of the reporter to H(2)O(2), suggesting the potential role of HuR in the process. Lowering of endogenous HuR levels through knockdown of HuR by siRNA greatly reduced the inducability and half-life of Snail mRNA, which consequently inhibited the downregulation of E-cadherin by H(2)O(2). Our findings indicate that HuR plays a major role in regulating H(2)O(2)-induced Snail expression by enhancing Snail mRNA stability, which in turn enhances cell migrating ability through repressing expression of E-cadherin.
Dong
Rui
R
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
Lu
Jian-Guo
JG
Wang
Qing
Q
He
Xian-Li
XL
Chu
Yan-Kui
YK
Ma
Qing-Jiu
QJ
D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000954:Antigens, Surface; D015820:Cadherins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D016877:Oxidants; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D006861:Hydrogen Peroxide