MIRNAS EXPRESSION PROFILING IN A WELL KNOWN MOUSE MODEL OF CANCER PROGRESSION ALLOWED THE IDENTIFICATION OF A MIRNA IMPLICATED IN THE INVASION-METASTASIS CASCADE

miRNAs are involved in the regulation of either physiological and pathological human processes. Several studies have investigated their role in cancer progression, but few works have found a general alteration in specific miRNAs which could be extended to different types of cancer. In order to identify an altered miRNAs expression profile during the different steps of cancer progression, especially in activation of the angiogenic switch, local invasion and onset of metastasis at a distant organ, we investigated miRNAs expression in a well known mouse model of tumorigenesis, the RIP-TAg mouse. The analysis revealed that a specific miRNA was constantly down-regulated during all stages of tumorigenesis compared to normal tissue. We showed that ectopic expression of this miRNA in breast cancer cell lines, MDAMB231 and MCF-7, inhibited anoikis-resistance, their migratory and invasive capacities in vitro, whereas its inhibition in the normal HMEC cells elicited aggressive features. Moreover, we demonstrated that down-regulation of this miRNA is a conserved mechanism of cancer progression towards metastatic phenotype in patients affected by advanced cancers, such as colon, breast, lung and gastric adenocarcinoma. We identified two targets of this miRNA. Their role in cancer is controversial but several evidences implicate them in cancer progression and in promoting cell oriented migration. Importantly, we demonstrated that both miRNA and its targets levels are predictors of tumor recurrence in hepatocellular carcinoma patients. Thus, this study revealed that this miRNA is lost during tumor progression in different types of cancer and is able to predict tumor relapse.