miR-448 suppresses proliferation and invasion by regulating IGF1R in colorectal cancer cells.

Accumulating evidence has demonstrated that miR-448 expression was downregulated, and exerted tumor suppressor roles in several types of cancer. However, the biological function and underlying mechanism of miR-448 in colorectal cancer (CRC) have not been elucidated. In this study, we detected the miR-448 expression in CRC tumor tissues and adjacent normal tissues (ANT) and five colorectal cancer cell lines by real time quantitative RT-PCR (qRT-PCR). Cell proliferation, colony formation, migration and invasion were investigated in CRC cells transfected miR-448 mimic or negative control mimic by MTT, colony forming, wound healing and transwell invasion assays, respectively. Target gene was identified by bioinformatic prediction, dual-luciferase reporter assay, qRT-PCR and Western blot. Our data proved that miR-448 expression was downregulated in CRC tissues and cell lines, and was inversely associated with advanced tumor-node-metastasis (TNM) stage (P < 0.01), and lymph node metastasis (P < 0.01). Overexpression of miR-448 suppressed CRC cell proliferation, colony formation, migration, and invasion. Moreover, we identified insulin-like growth factor 1 receptor (IGF1R) as a direct target gene of miR-448 in CRC cell. IGF1R expression was upregulated in CRC tissues and cell lines, and its expression was negatively correlated with the expression level of miR-448 in CRC tissues(r = -0.569, P = 0.002). In addition, IGF1R overexpression rescued the suppressive effect of miR-448-mediated CRC on cell proliferation, colony formation, migration and invasion. These results suggested that miR-448 might serve as a tumor suppressor in CRC partly through targeting IGF1R.