TY - JOUR
AU - Laudato, Sara
AU - Patil, Nitin Shaligram
AU - Abba, Mohammed Lawan
AU - Leupold, Joerg H
AU - Benner, Axel
AU - Gaiser, Timo
AU - Marx, Alexander
AU - Allgayer, Heike
TI - P53-induced miR-30e-5p inhibits colorectal cancer invasion and metastasis by targeting ITGA6 and ITGB1.
JO - International journal of cancer
VL - 141
IS - 9
SN - 0020-7136
CY - Bognor Regis
PB - Wiley-Liss
M1 - DKFZ-2017-04102
SP - 1879 - 1890
PY - 2017
AB - 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.
LB - PUB:(DE-HGF)16
C6 - pmid:28656629
DO - DOI:10.1002/ijc.30854
UR - https://inrepo02.dkfz.de/record/128080
ER -