کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10899321 | 1084363 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/β-catenin signaling pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/β-catenin signaling pathway Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/β-catenin signaling pathway](/preview/png/10899321.png)
چکیده انگلیسی
The Wnt/β-catenin pathway is known to contribute to colorectal cancer (CRC) progression, although little is known about the contribution of β-catenin on this process. We investigated the role of miR-490-3p, which was recently reported to suppress tumorigenesis through its effect on Wnt/β-catenin signaling. We found that hypermethylation of the miR-490-3p promoter down-regulates miR-490-3p expression in CRC tissue. Gain- and loss-of-function assays in vitro and in vivo reveal that miR-490-3p suppresses cancer cell proliferation by inducing apoptosis and inhibits cell invasiveness by repressing the initiation of epithelial-to-mesenchymal transition (EMT), a key mechanism in cancer cell invasiveness and metastasis. The frequently rearranged in advanced T-cell lymphomas (FRAT1) protein was identified as a direct target of miR-490-3p and contributes to its tumor-suppressing effects. miR-490-3p appears to have an inhibitory effect on β-catenin expression in nuclear fractions of CRC cells, whereas FRAT1 expression is associated with the accumulation of β-catenin in the nucleus of cells, which could be weakened by transfection with miR-490-3p. Our findings suggest that the miR-490-3p/FRAT1/β-catenin axis is important in CRC progression and provides new insight into the molecular mechanisms underlying CRC. They may help to confirm the pathway driving CRC aggressiveness and serve for the development of a novel miRNA-targeting anticancer therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 376, Issue 1, 28 June 2016, Pages 178-187
Journal: Cancer Letters - Volume 376, Issue 1, 28 June 2016, Pages 178-187
نویسندگان
Kehong Zheng, Xinying Zhou, Jinlong Yu, Qiang Li, Hui Wang, Mingyi Li, Ziyun Shao, Feifei Zhang, Yuhao Luo, Zetao Shen, Fei Chen, Fujun Shi, Chunhui Cui, Dachuan Zhao, Zhiqun Lin, Wei Zheng, Zhaowei Zou, Zonghai Huang, Liang Zhao,