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

• Verfasst von: Laudato, Sara [VerfasserIn]
• Verfasst von: Patil, Nitin [VerfasserIn]
• Verfasst von: Abba, Mohammed L. [VerfasserIn]
• Verfasst von: Leupold, Jörg [VerfasserIn]
• Verfasst von: Gaiser, Timo [VerfasserIn]
• Verfasst von: Marx, Alexander [VerfasserIn]
• Verfasst von: Allgayer, Heike [VerfasserIn]
• Titel: P53-induced miR-30e-5p inhibits colorectal cancer invasion and metastasis by targeting ITGA6 and ITGB1
• Verf.angabe: Sara Laudato, Nitin Patil, Mohammed L. Abba, Joerg H. Leupold, Axel Benner, Timo Gaiser, Alexander Marx and Heike Allgayer
• Umfang: 12 S.
• Fussnoten: Gesehen am 27.06.2018
• Titel Quelle: Enthalten in: International journal of cancer
• Jahr Quelle: 2017
• Band/Heft Quelle: 141(2017), 9, S. 1879-1890
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.30854
• Sprache: eng
• K10plus-PPN: 1576919676

Abstract

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.