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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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2017
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| In: |
International journal of cancer
Year: 2017, Jahrgang: 141, Heft: 9, Pages: 1879-1890 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.30854 |
| Online-Zugang: | 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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| Verfasserangaben: | Sara Laudato, Nitin Patil, Mohammed L. Abba, Joerg H. Leupold, Axel Benner, Timo Gaiser, Alexander Marx and Heike Allgayer |
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| 245 | 1 | 0 | |a P53-induced miR-30e-5p inhibits colorectal cancer invasion and metastasis by targeting ITGA6 and ITGB1 |c Sara Laudato, Nitin Patil, Mohammed L. Abba, Joerg H. Leupold, Axel Benner, Timo Gaiser, Alexander Marx and Heike Allgayer |
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| 520 | |a 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. | ||
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