miR-320a suppresses colorectal cancer progression by targeting Rac1
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en ciblant le gène Rac1, le micro-ARN miR-320a exerce une fonction de suppresseur de tumeurs dans le cancer colorectal
MicroRNAs (miRNAs) have emerged as critical epigenetic regulators involved in cancer progression. miR-320a has been identified to be a novel tumour suppressive miRNA in colorectal cancer (CRC). However, the detailed molecular mechanisms are not fully understood. Here, we reported that miR-320a inversely associated with CRC aggressiveness in both cell lines and clinical specimens. Functional studies demonstrated that miR-320a significantly decreased the capability of cell migration/invasion and induced G0/G1 growth arrest in vitro and in vivo. Furthermore, Rac1 was identified as one of the direct downstream targets of miR-320a and miR-320a specifically binds to the conserved 8mer at position 1140-1147 of Rac1 3’-untranslated region (3’-UTR) to regulate Rac1 protein expression. Over-expression of miR-320a in SW620 cells inhibited Rac1 expression while reduction of miR-320a by anti-miR-320a in SW480 cells enhanced Rac1 expression. Re-expression of Rac1 in the SW620/miR-320a cells restored the cell migration/invasion inhibited by miR-320a, whereas knockdown of Rac1 in the SW480/anti-miR-320a cells repressed these cellular functions elevated by anti-miR-320a. Conclusively, our results demonstrate that miR-320a functions as a tumour suppressive miRNA through targeting Rac1 in CRC.
http://carcin.oxfordjournals.org/content/early/2013/11/19/carcin.bgt378.abstract