Lu GuiFeng, Sun YaLing, An ShengLi, Xin SaiNan, Ren XiaoLi, Zhang Dan, Wu PingXiang, Liao WenTing, Ding YanQing, Liang Li
Department of Pathology, Southern Medical University, Guangzhou City 510515, Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Clinical Medical College, Southern Medical University, Guangzhou City 510515, Guangdong Province, People's Republic of China.
Exp Mol Pathol. 2015 Aug;99(1):173-9. doi: 10.1016/j.yexmp.2015.06.014. Epub 2015 Jun 20.
Colorectal cancer (CRC) is one of the most common malignancies. Increasing evidences indicate that dysregulation of miRNAs is a frequent event in CRC and contributes to the pathogenesis of CRC. In this study, we found that over-expression of miR-34a inhibited cell proliferation and invasion, induced a cell cycle arrest and triggered apoptosis, while knockdown of miR-34a showed the opposite effects. Moreover, ectopic miR-34a suppressed tumor growth and metastasis of CRC cells in vivo. FMNL2 and E2F5 were identified as direct targets of miR-34a. Reintroduction of FMNL2 or E2F5 without 3'UTR region reversed the inhibitory effects of miR-34a on cell proliferation and invasion. MiR-34a was down-regulated in CRC cells and inversely correlated with FMNL2 and E2F5 expressions. Our study suggests that miR-34a is an important tumor suppressor of CRC progression by targeting FMNL2 and E2F5, thus providing new insight into the molecular mechanisms underlying CRC progression and establishing a strong potential for the application of miR-34a as a novel therapeutic marker against CRC.
结直肠癌（CRC）是最常见的恶性肿瘤之一。越来越多的证据表明，miRNA的失调在CRC中是常见事件，并促成了CRC的发病机制。在本研究中，我们发现miR-34a的过表达抑制细胞增殖和侵袭，诱导细胞周期停滞并引发凋亡，而敲低miR-34a则显示出相反的效果。此外，异位表达的miR-34a在体内抑制CRC细胞的肿瘤生长和转移。FMNL2和E2F5被鉴定为miR-34a的直接靶点。重新导入不含3'UTR区域的FMNL2或E2F5可逆转miR-34a对细胞增殖和侵袭的抑制作用。miR-34a在CRC细胞中表达下调，且与FMNL2和E2F5的表达呈负相关。我们的研究表明，miR-·34a通过靶向FMNL2和E2F5是CRC进展的重要肿瘤抑制因子，从而为CRC进展的分子机制提供了新见解，并为将miR-34a作为抗CRC的新型治疗标志物应用奠定了强大潜力。
