MicroRNA-93 suppress colorectal cancer development via Wnt/β-catenin pathway downregulating
MicroRNA-93 suppress colorectal cancer development via Wnt/β-catenin pathway downregulating
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DOI：
10.1007/s13277-014-2771-6
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发表时间：
2015-03-01
期刊：
影响因子：
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通讯作者：
Wang, Xishan
中科院分区：
文献类型：
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作者：
Tang, Qingchao;Zou, Zhaoxia;Wang, Xishan
MicroRNA-93 （miR-93）参与多种癌症进展。据报道，miR-93在不同的肿瘤中作为启动子或抑制子。然而，到目前为止，miR-93在结肠癌中的作用尚不清楚。我们发现miR-93在人结肠癌组织和结直肠癌细胞系中的表达较正常结肠粘膜低。在结肠癌细胞中强制表达miR-93可以抑制结肠癌的侵袭、迁移和增殖。此外，miR-93可能下调Wnt/ β -catenin通路，通过测量该通路中β -catenin、axin、c-Myc和cyclin-D1的表达水平证实了这一点。Smad7 （Mothers against decapentaplegic homolog 7）是典型Wnt信号通路中β -catenin核积累的重要分子蛋白，通过silico方法预测其可能是miR-93的靶基因，并证明其可通过靶向其3'UTR来抑制。这些发现表明，miR-93通过下调Wnt/ β -连环蛋白来抑制结直肠癌的发展，至少部分是通过靶向Smad7。本研究揭示了miR-93在结肠癌中是一个重要的负调节因子，提示miR-93可能作为一种新的治疗药物，为结肠癌的治疗提供益处。
MicroRNA-93 (miR-93) is involved in several carcinoma progressions. It has been reported that miR-93 acts as a promoter or suppressor in different tumors. However, till now, the role of miR-93 in colon cancer is unclear. Herein, we have found that expression of miR-93 was lower in human colon cancer tissue and colorectal carcinoma cell lines compared with normal colon mucosa. Forced expression of miR-93 in colon cancer cells inhibits colon cancer invasion, migration, and proliferation. Furthermore, miR-93 may downregulate the Wnt/beta-catenin pathway, which was confirmed by measuring the expression level of the beta-catenin, axin, c-Myc, and cyclin-D1 in this pathway. Mothers against decapentaplegic homolog 7 (Smad7), as an essential molecular protein for nuclear accumulation of beta-catenin in the canonical Wnt signaling pathway, is predicted as a putative target gene of miR-93 by the silico method and demonstrated that it may be suppressed by targeting its 3'UTR. These findings showed that miR-93 suppresses colorectal cancer development via downregulating Wnt/beta-catenin, at least in part, by targeting Smad7. This study revealed that miR-93 is an important negative regulator in colon cancer and suggested that miR-93 may serve as a novel therapeutic agent that offers benefits for colon cancer treatment.