Clinical and biological significance of miR-378a-3p and miR-378a-5p in colorectal cancer.

To investigate miR-378a-3p and miR-378a-5p expression and their relationships with the clinicopathological features of colorectal cancer (CRC). Our results showed that miR-378a-3p and miR-378a-5p expression were dramatically lower in CRC cell lines and tissues than that in adjacent normal colorectal mucosal tissues, respectively. MiR-378a-3p and miR-378a-5p expression were significantly associated with histological differentiation and TNM stage, respectively. CRC patients with low miR-378a-3p and miR-378a-5p expression had a significantly shorter survival time than those patients with high miR-378a-3p and miR-378a-5p expression (p<0.001, p<0.001), respectively. Univariate and multivariable Cox regression analysis showed that tumour size, TNM stage, miR-378a-3p expression and miR-378a-5p expression were independent prognostic factors for CRC patients. Ectopic miR-378a-3p or miR-378a-5p expression inhibited cellular proliferation and colony formation, induced apoptosis and G1-phase cell cycle arrest in CRC cells, but had no effect on migration and invasion of CRC cells. Furthermore, miR-378a-3p over-expression or down-regulation could inhibit or enhance insulin-like growth factor 1 receptor (IGF1R) expression in CRC cells. There was a significantly negative correlation between IGF1R protein expression and miR-378a-3p expression in CRC tissues. MiR-378a-3p over-expression or down-regulation suppressed or enhanced phosphorylated-ERK1/2 protein level, but had no effect on phosphorylated-Akt protein level. In conclusion, miR-378a-3p and miR-378a-5p expression might play an important role as tumour suppressor gene in the initial stage of carcinogenesis of CRC.