Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and… Click to show full abstract
Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be down-regulated in CRC patients with liver metastases compared to those without (P = 0.025, Fold Change = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival time (33.3 months vs. 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced TNM staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by Exo miR-150. Target-prediction assessment and dual luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.
               
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