Deng Biao, Wang Bin, Fang Jiaqing, Zhu Xuchao, Cao Zhongwei, Lin Qi, Zhou Lisheng, Sun Xing
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
Department of Gastroenterology, Tianyou Hospital, TongJi University, 500 Zhennan Road, Shanghai, 200331, China.
Sci Rep. 2016 Jul 4;6:28301. doi: 10.1038/srep28301.
While it is known that miR-203 is frequently downregulated in many types of human cancer, little is known regarding its expression and functional role in colorectal cancer (CRC). In this study, we aimed to investigate the expression and the potential mechanisms of miR-203 in colorectal cancer. MiR-203 was significantly downregulated in CRC tissues compared with matched normal adjacent tissues. Our clinical data show that decreased miR-203 was associated with an advanced clinical tumor-node-metastasis stage, lymph node metastasis, and poor survival in CRC patients. Furthermore, externally induced expression of miR-203 significantly inhibited CRC cell proliferation and invasion in vitro and in vivo. Mechanistically, we identified EIF5A2 as a direct and functional target of miR-203. The levels of miR-203 were inversely correlated with levels of the EIF5A2 in the CRC tissues. Restoration of EIF5A2 in the miR-203-overexpressing CRC cells reversed the suppressive effects of miR-203. Our results demonstrate that miR-203 serves as a tumor suppressor gene and may be useful as a new potential therapeutic target in CRC.
虽然已知miR-203在多种人类癌症中经常下调，但关于其在结直肠癌（CRC）中的表达和功能作用知之甚少。在本研究中，我们旨在研究miR-203在结直肠癌中的表达及潜在机制。与配对的正常相邻组织相比，miR-203在CRC组织中显著下调。我们的临床数据表明，miR-203降低与CRC患者的临床肿瘤-淋巴结-转移晚期、淋巴结转移及不良生存相关。此外，外源性诱导miR-203表达在体外和体内均显著抑制CRC细胞增殖和侵袭。机制上，我们确定EIF5A2是miR-203的直接功能靶点。CRC组织中miR-203水平与EIF5A2水平呈负相关。在miR-203过表达的CRC细胞中恢复EIF5A2可逆转miR-203的抑制作用。我们的结果表明，miR-203作为一种肿瘤抑制基因，可能作为CRC新的潜在治疗靶点。
