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 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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