MicroRNA-185 is a novel tumor suppressor by negatively modulating the Wnt/β-catenin pathway in human colorectal cancer
MicroRNA-185 is a novel tumor suppressor by negatively modulating the Wnt/β-catenin pathway in human colorectal cancer
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DOI：
10.4103/0019-509x.186576
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发表时间：
2015-12-01
影响因子：
1
通讯作者：
Su-juan, Z.
中科院分区：
文献类型：
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作者：
Dong-xu, W.;Jia, L.;Su-juan, Z.
目的：microRNA-185(miR-185)基因失控与多种肿瘤相关，并在多种人类恶性肿瘤中发挥肿瘤抑制作用。因此，我们试图找出它在人类结直肠癌(CRC)中的作用。材料和方法：用实时荧光定量聚合酶链式反应检测MIR-185的表达。我们进行了miR-185的过表达或用模拟物或抑制剂分别敲除miR-185的转染。用细胞计数Kit-8法等功能检测细胞增殖情况。为了研究miR-185对Wnt/-catenin信号通路的影响，我们进一步应用了荧光素酶报告基因分析和Western blotting对该途径中的特定蛋白进行了检测。结果：与相应的对照细胞株相比，结直肠癌细胞系MIR-185表达下调。我们还证明了它在LoVo细胞中的过表达能够显着地抑制细胞的增殖，而在SW480细胞中过表达则具有相反的作用。我们从机制上证明了miR-185可以抑制Wnt/-catenin信号通路，并调节该通路下游分子的转录和翻译水平，包括MYC和CCND1。结论：这些结果提示miR-185可能通过负向调节Wnt/-catenin途径发挥其抑瘤作用。
OBJECTIVE: The deregulation of microRNA-185 (miR-185) has been showed to be associated with many cancers and act as a tumor suppressor in many types of human malignancies. We hence tried to find out its role in human colorectal cancer (CRC). MATERIALS AND METHODS: miR-185 expression was investigated by real-time quantitative polymerase chain reaction. We carried out transfections to overexpress or knockdown of miR-185 by mimics or inhibitor, respectively. Functional study like cell counting kit-8 assay was performed to evaluate the proliferation. For addressing the impact of miR-185 on Wnt/-catenin signaling, we further applied luciferase reporter assay and Western blotting for specific proteins in this pathway. RESULTS: miR-185 was decreased in CRC cell lines when compared with corresponding control cell line. We also proved that its overexpression in LoVo cells could remarkably suppress cell proliferation whereas knocked it down in SW480 cells has the opposite effect in vitro. Mechanically, we demonstrated that miR-185 could suppress the Wnt/-catenin signaling and modulate the transcription and translation level of downstream molecules of this pathway, including MYC and CCND1. CONCLUSION: Taken together, these results suggested that miR-185 exerts its tumor suppressor activities probably through a negative modulation of the Wnt/-catenin pathway.