MACC1基因对肿瘤生长转移具有明显促进作用。研究提示，结直肠癌生长转移进程中可能存在以MACC1为主的分子调控网络。对该网络的探索鉴定具有重要临床意义。micrRNA通过负性调控靶基因参与调控肿瘤的发生发展，而其自身表达也受上游分子调节。本研究旨在鉴定结直肠癌中受MACC1调控的microRNA及其下游靶基因和效应信号途径。在前期研究中，我们采用microRNA芯片检测了敲低MACC1表达前后的microRNA表达谱变化，发现miR-320a/b随MACC1降低而表达上调，且二者在结直肠癌组织中的表达显著低于正常肠粘膜。因此我们推测MACC1对miR-320a/b具有负性调控作用。本研究中，我们将验证MACC1对miR-320a/b的转录调控，鉴定miR-320a/b的下游靶基因及相关信号途径，明确“MACC1—miR-320a/b—靶基因”这一调控关系在结直肠癌生长转移过程中的作用。

MACC1 has been described to promote tumor progression in colorectal cancer (CRC). However, the molecular mechanism underlying it remains unclear. MicroRNAs function as oncogenes or tumor suppressors by negatively regulating target genes, while their expression is mediated by upstream signalings.The aim of this study is to identify microRNAs that are directly regulated by MACC1 in CRC, detect their potential target genes and downstream signaling pathways. Our preliminary data obtained from microRNA array showed that, miR-320a/b, which are lowly expressed in CRC tissues, were significantly up-regulated in MACC1-knockdown CRC cells compared with scramble control. We thus speculated that they may be negatively regulated by MACC1 in CRC. In this study, we attempt to identify if MACC1 could regulate miR-320a/b at transcription level by using luciferase reporter assay and chromosome immunoprecipitation assay. Immunoblotting and real time-PCR will be conducted to valdiate the direct target genes of miR-320a/b. Furthermore, we will perform gain- or loss-of-function assays to demonstrate the functional effects of miR-320a/b on MACC1-mediated tumor progression of CRC.