MicroRNA-194 modulates epithelial-mesenchymal transition in human colorectal cancer metastasis.

MicroRNA-194 modulates epithelial-mesenchymal transition in human colorectal cancer metastasis.
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DOI:
10.2147/ott.s125172
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发表时间:
2017
影响因子:
4
通讯作者:
Deng YC
Deng YC
中科院分区:
医学3区
文献类型:
--
作者:
Cai HK;Chen X;Tang YH;Deng YC

文献摘要

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MicroRNAs(MiRNAs)作为基因表达的关键调控因子,与肿瘤的发生发展密切相关。MIR-194已被证明是多种癌症的肿瘤调控因子,但其在结直肠癌中的生物学功能和作用机制尚未得到很好的研究。在本研究中,我们发现miR-194在结直肠癌临床标本中的表达上调,而miR-194的过表达促进了结直肠癌细胞的迁移和侵袭。此外,miR-194通过下调E-钙粘附素的表达(P<0.01),上调波形蛋白和基质金属蛋白酶-2的表达(P<0.001,P<0.05),显著影响上皮-间充质转化的标志物。细胞迁移是与肌动蛋白细胞骨架相关的细胞运动。在本研究中,我们发现miR-194增加了SW480细胞的细胞极化。此外,酶谱分析显示miR-194显著上调了明胶降解活性(P<0.01)。总之,我们的发现提示miR-194在结直肠癌中作为肿瘤促进剂发挥作用,这可能为结直肠癌的发展和转移的研究提供新的见解。
MicroRNAs (miRNAs), as key regulators of gene expression, are closely related to tumor occurrence and progression. MiR-194 has been proved as a tumor regulatory factor in various cancers; however, the biological function and mechanism of action in colorectal cancer (CRC) have not been well explored. In the present study, we found that miR-194 expression is upregulated in CRC clinical specimens, while overexpression of miR-194 promotes cell migration and invasion in CRC cell lines. Besides, miR-194 significantly influenced the epithelial–mesenchymal transition (EMT) markers by downregulating E-cadherin expression (P<0.01) and upregulating vimentin and MMP-2 expression (P<0.001, P<0.05). Cell migration is the cell movement related to actin cytoskeleton. In this study, we found miR-194 increased cell polarization in SW480 cells. Moreover, zymography assay showed that miR-194 significantly upregulated the gelatin-degrading activity of MMP-2 (P<0.01). Collectively, our findings suggest that miR-194 functions as a tumor promoter in CRC, which may provide new insights for the study of CRC development and metastasis.