OCT4 as a target of miR-34a stimulates p63 but inhibits p53 to promote human cell transformation.

W. L. Ng, G. Chen, M. Wang, H. Wang, M. Story, J. W. Shay, X. Zhang, J. Wang, A. R. Amin, B. Hu, F. A. Cucinotta, Y. Wang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Human cell transformation is a key step for oncogenic development, which involves multiple pathways; however, the mechanism remains unclear. To test our hypothesis whether cell oncogenic transformation shares some mechanisms with the process of reprogramming non-stem cells to induced pluripotent stem cells (iPSC), we studied the relationship among the key factors for promoting or inhibiting iPSC in radiation-transformed human epithelial cell lines derived from different tissues (lung, breast and colon). We unexpectedly found that p63 and OCT4 were highly expressed (accompanied by low expressed p53 and miR-34a) in all transformed cell lines examined when compared with their non-transformed counterparts. We further elucidated the relationship of these factors: the 3p strand of miR-34a directly targeted OCT4 by binding to the 3' untranslated region (3'-UTR) of OCT4 and, OCT4, in turn, stimulated p63 but inhibited p53 expression by binding to a specific region of the p63 or p53 promoter. Moreover, we revealed that the effects of OCT4 on promoting cell oncogenic transformation were by affecting p63 and p53. These results support that a positive loop exists in human cells: OCT4 upregulation as a consequence of inhibition of miR-34a, promotes p63 but suppresses p53 expression, which further stimulates OCT4 upregulation by downregulating miR-34a. This functional loop contributes significantly to cell transformation and, most likely, also to the iPSC process.

Original languageEnglish (US)
JournalCell death & disease
Volume5
DOIs
StatePublished - 2014

Fingerprint

Induced Pluripotent Stem Cells
Up-Regulation
Transformed Cell Line
3' Untranslated Regions
Colon
Breast
Down-Regulation
Epithelial Cells
Radiation
Cell Line
Lung

ASJC Scopus subject areas

  • Medicine(all)

Cite this

OCT4 as a target of miR-34a stimulates p63 but inhibits p53 to promote human cell transformation. / Ng, W. L.; Chen, G.; Wang, M.; Wang, H.; Story, M.; Shay, J. W.; Zhang, X.; Wang, J.; Amin, A. R.; Hu, B.; Cucinotta, F. A.; Wang, Y.

In: Cell death & disease, Vol. 5, 2014.

Research output: Contribution to journalArticle

Ng, W. L. ; Chen, G. ; Wang, M. ; Wang, H. ; Story, M. ; Shay, J. W. ; Zhang, X. ; Wang, J. ; Amin, A. R. ; Hu, B. ; Cucinotta, F. A. ; Wang, Y. / OCT4 as a target of miR-34a stimulates p63 but inhibits p53 to promote human cell transformation. In: Cell death & disease. 2014 ; Vol. 5.
@article{3486634c93a146c3bfd1310c018b3bb3,
title = "OCT4 as a target of miR-34a stimulates p63 but inhibits p53 to promote human cell transformation.",
abstract = "Human cell transformation is a key step for oncogenic development, which involves multiple pathways; however, the mechanism remains unclear. To test our hypothesis whether cell oncogenic transformation shares some mechanisms with the process of reprogramming non-stem cells to induced pluripotent stem cells (iPSC), we studied the relationship among the key factors for promoting or inhibiting iPSC in radiation-transformed human epithelial cell lines derived from different tissues (lung, breast and colon). We unexpectedly found that p63 and OCT4 were highly expressed (accompanied by low expressed p53 and miR-34a) in all transformed cell lines examined when compared with their non-transformed counterparts. We further elucidated the relationship of these factors: the 3p strand of miR-34a directly targeted OCT4 by binding to the 3' untranslated region (3'-UTR) of OCT4 and, OCT4, in turn, stimulated p63 but inhibited p53 expression by binding to a specific region of the p63 or p53 promoter. Moreover, we revealed that the effects of OCT4 on promoting cell oncogenic transformation were by affecting p63 and p53. These results support that a positive loop exists in human cells: OCT4 upregulation as a consequence of inhibition of miR-34a, promotes p63 but suppresses p53 expression, which further stimulates OCT4 upregulation by downregulating miR-34a. This functional loop contributes significantly to cell transformation and, most likely, also to the iPSC process.",
author = "Ng, {W. L.} and G. Chen and M. Wang and H. Wang and M. Story and Shay, {J. W.} and X. Zhang and J. Wang and Amin, {A. R.} and B. Hu and Cucinotta, {F. A.} and Y. Wang",
year = "2014",
doi = "10.1038/cddis.2013.563",
language = "English (US)",
volume = "5",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - OCT4 as a target of miR-34a stimulates p63 but inhibits p53 to promote human cell transformation.

AU - Ng, W. L.

AU - Chen, G.

AU - Wang, M.

AU - Wang, H.

AU - Story, M.

AU - Shay, J. W.

AU - Zhang, X.

AU - Wang, J.

AU - Amin, A. R.

AU - Hu, B.

AU - Cucinotta, F. A.

AU - Wang, Y.

PY - 2014

Y1 - 2014

N2 - Human cell transformation is a key step for oncogenic development, which involves multiple pathways; however, the mechanism remains unclear. To test our hypothesis whether cell oncogenic transformation shares some mechanisms with the process of reprogramming non-stem cells to induced pluripotent stem cells (iPSC), we studied the relationship among the key factors for promoting or inhibiting iPSC in radiation-transformed human epithelial cell lines derived from different tissues (lung, breast and colon). We unexpectedly found that p63 and OCT4 were highly expressed (accompanied by low expressed p53 and miR-34a) in all transformed cell lines examined when compared with their non-transformed counterparts. We further elucidated the relationship of these factors: the 3p strand of miR-34a directly targeted OCT4 by binding to the 3' untranslated region (3'-UTR) of OCT4 and, OCT4, in turn, stimulated p63 but inhibited p53 expression by binding to a specific region of the p63 or p53 promoter. Moreover, we revealed that the effects of OCT4 on promoting cell oncogenic transformation were by affecting p63 and p53. These results support that a positive loop exists in human cells: OCT4 upregulation as a consequence of inhibition of miR-34a, promotes p63 but suppresses p53 expression, which further stimulates OCT4 upregulation by downregulating miR-34a. This functional loop contributes significantly to cell transformation and, most likely, also to the iPSC process.

AB - Human cell transformation is a key step for oncogenic development, which involves multiple pathways; however, the mechanism remains unclear. To test our hypothesis whether cell oncogenic transformation shares some mechanisms with the process of reprogramming non-stem cells to induced pluripotent stem cells (iPSC), we studied the relationship among the key factors for promoting or inhibiting iPSC in radiation-transformed human epithelial cell lines derived from different tissues (lung, breast and colon). We unexpectedly found that p63 and OCT4 were highly expressed (accompanied by low expressed p53 and miR-34a) in all transformed cell lines examined when compared with their non-transformed counterparts. We further elucidated the relationship of these factors: the 3p strand of miR-34a directly targeted OCT4 by binding to the 3' untranslated region (3'-UTR) of OCT4 and, OCT4, in turn, stimulated p63 but inhibited p53 expression by binding to a specific region of the p63 or p53 promoter. Moreover, we revealed that the effects of OCT4 on promoting cell oncogenic transformation were by affecting p63 and p53. These results support that a positive loop exists in human cells: OCT4 upregulation as a consequence of inhibition of miR-34a, promotes p63 but suppresses p53 expression, which further stimulates OCT4 upregulation by downregulating miR-34a. This functional loop contributes significantly to cell transformation and, most likely, also to the iPSC process.

UR - http://www.scopus.com/inward/record.url?scp=84906911102&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906911102&partnerID=8YFLogxK

U2 - 10.1038/cddis.2013.563

DO - 10.1038/cddis.2013.563

M3 - Article

C2 - 24457968

AN - SCOPUS:84906911102

VL - 5

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

ER -