MicroRNA-143 Targets MACC1 to Inhibit Cell Invasion and Migration in Colorectal cancer

Using both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues.Our findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in western countries [1], with very poor prognosis and high possibilities of tumor invasion and migration. Although invasion and migration have been acknowledged as the most lethal attributes of solid tumors, the molecular mechanism underlying them is still limited.Recently, growing evidences have supported the cancer-related effects of miRNAs, a newly discovered class of non-coding small RNA which functions through negatively regulating a variety of gene expression. Mature miRNAs exert effects by integrating into an RNA-inducing silencing complex (RISC) and binding to specific complementary sites within 3' untranslated regions (3'UTR) of their target genes mRNA, to inhibit translation or directly induce degradation [2-5]. Bioinformatic algorithms assess that all the human miRNAs may regulate up to 30% of human genes which represent the majority of gene