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P53-induced miR-30e-5p inhibits colorectal cancer invasion and metastasis by targeting ITGA6 and ITGB1

The tumor suppressor P53 is a critical regulator of normal cellular homeostasis whose function is either distorted or lost in several cancer types including colorectal cancer (CRC). A small group of microRNAs have come to be recognized as essential mediators of P53 function. In a genome-wide systema...

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Main Authors: Laudato, Sara (Author) , Patil, Nitin (Author) , Abba, Mohammed L. (Author) , Leupold, Jörg (Author) , Gaiser, Timo (Author) , Marx, Alexander (Author) , Allgayer, Heike (Author)
Format: Article (Journal)
Language:English
Published: 2017
In: International journal of cancer
Year: 2017, Volume: 141, Issue: 9, Pages: 1879-1890
ISSN:1097-0215
DOI:10.1002/ijc.30854
Online Access:Verlag, Volltext: http://dx.doi.org/10.1002/ijc.30854
Verlag, Volltext: http://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.30854
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Author Notes:Sara Laudato, Nitin Patil, Mohammed L. Abba, Joerg H. Leupold, Axel Benner, Timo Gaiser, Alexander Marx and Heike Allgayer
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Summary:The tumor suppressor P53 is a critical regulator of normal cellular homeostasis whose function is either distorted or lost in several cancer types including colorectal cancer (CRC). A small group of microRNAs have come to be recognized as essential mediators of P53 function. In a genome-wide systematic approach, we explored miRNAs that are substantially altered by P53 loss and found miR-30e to be the most significantly deregulated miRNA in P53-knockout human CRC cells. We identified miR-30e-5p to be a novel direct transcriptional target of P53 with gain and loss of function experiments revealing miR-30e-5p to be a significant regulator of tumor cell migration, invasion and in vivo metastasis mediated in part by integrins alpha-6 and beta-1 as novel targets. MiR-30e-5p also significantly reduced tumor cell proliferation by causing G1/S cell cycle arrest, which was achieved by inducing P21 and P27 expression. Finally, we found miR-30e-5p to be lost in resected CRC tumors as compared to normal colon tissues. Taken together, miR-30e-5p is a novel effector of P53-induced suppression of migration, invasion and metastasis.
Item Description:Gesehen am 27.06.2018
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.30854

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