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  • Title: P53-induced miR-30e-5p inhibits colorectal cancer invasion and metastasis by targeting ITGA6 and ITGB1.
    Author: Laudato S, Patil N, Abba ML, Leupold JH, Benner A, Gaiser T, Marx A, Allgayer H.
    Journal: Int J Cancer; 2017 Nov 01; 141(9):1879-1890. PubMed ID: 28656629.
    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.
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