MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2.
MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2.
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miRNA-203 通过靶向 EIF5A2 抑制结直肠癌的细胞增殖、迁移和侵袭。
DOI：
10.1038/srep28301
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发表时间：
2016-07-04
影响因子：
4.6
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Deng B;Wang B;Fang J;Zhu X;Cao Z;Lin Q;Zhou L;Sun X
虽然已知miR-203在许多类型的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。本研究旨在探讨miR-203在结直肠癌中的表达及其可能机制。miR-203在结直肠癌组织中的表达明显低于癌旁正常组织。我们的临床数据显示，miR-203减少与CRC患者的晚期临床肿瘤淋巴结转移阶段、淋巴结转移和不良生存率相关。此外，外部诱导的miR-203表达在体外和体内显著抑制CRC细胞增殖和侵袭。从机制上讲，我们将EIF 5A 2鉴定为miR-203的直接和功能性靶点。CRC组织中miR-203的水平与EIF 5A 2的水平呈负相关。在miR-203过表达的CRC细胞中恢复EIF 5A 2逆转了miR-203的抑制作用。我们的研究结果表明，miR-203作为一种肿瘤抑制基因，可能是一个新的潜在的治疗CRC的目标。
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.