MicroRNA-31 contributes to colorectal cancer development by targeting factor inhibiting HIF-1α (FIH-1)

摘要

The molecular mechanisms underlying colorectal cancer (CRC) tumorigenesis remain incompletely understood, partially contributing to the mortality of CRC. Advances in identification of novel mechanisms are therefore in an urgent need to fill the gap of our knowledge in CRC development. Here, we performed both in vitro and in vivo experiments along with in silico analysis to identify a new regulatory circuit that stimulated CRC tumorigenesis. In this report, we, for the first time, analyzed the correlation of FIH-1 level with clinicopathological features of CRC. The finding that FIH-1 was not only significantly decreased in tumor tissue as compared with the adjacent normal tissue but also was significantly correlated with tumor T stage status, indicated the role of FIH-1 as a tumor suppressor in CRC development. Moreover, we found the expression of miR-31, a short non-coding RNA which played a critical role in CRC development, was negatively correlated with FIH-1 expression in CRC samples and cell lines. Together with the result from luciferase report assay, it was demonstrated that miR-31 could directly regulate FIH-1 expression in CRC. This miR-31/FIH-1 nexus was further shown to control cell proliferation, migration and invasion in vitro and to control tumor growth in vivo. Additionally, correlation of the miR-31 expression with clinicopathologic features in CRC samples was examined in support of the driving role of newly identified miR-31/FIH-1 nexus in CRC tumorigenesis. These findings highlight the critical role of miR-31/FIH-1 nexus in CRC and reveal the contribution of miR-31 to CRC development by targeting FIH-1.