Title |
MiR-452 promotes an aggressive colorectal cancer phenotype by regulating a Wnt/β-catenin positive feedback loop
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Published in |
Journal of Experimental & Clinical Cancer Research, September 2018
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DOI | 10.1186/s13046-018-0879-z |
Pubmed ID | |
Authors |
Tingting Li, Xiangyu Jian, Han He, Qiuhua Lai, Xianzheng Li, Danling Deng, Tengfei Liu, Jiehong Zhu, Hongli Jiao, Yaping Ye, Shuyang Wang, Minhui Yang, Lin Zheng, Weijie Zhou, Yanqing Ding |
Abstract |
Aberrant activation of Wnt/β-catenin signaling pathway is considered to be an important issue in progression and metastasis of various human cancers, especially in colorectal cancer (CRC). MiR-452 could activate of Wnt/β-catenin signaling. But the mechanism remains unclear. The expression of miR-452 in CRC and normal tissues was detected by real-time quantitative PCR. The effect of miR-452 on CRC growth and invasion was conducted by functional experiments in vitro and in vivo. Bioinformatics and cell luciferase function studies verified the direct regulation of miR-452 on the 3'-UTR of the GSK3β, which leads to the activation of Wnt/β-catenin signaling. MiR-452 was upregulated in CRC compared with normal tissues and was correlated with clinical significance. The luciferase reporter system studies affirmed the direct regulation of miR-452 on the 3'-UTR of the GSK3β, which activate the Wnt/β-catenin signaling. The ectopic upregulation of miR-452 significantly inhibited the expression of GSK3β and enhanced CRC proliferation and invasion in vitro and in vivo. Meanwhile, knockdown of miR-452 significantly recovered the expression of GSK3β and attenuated Wnt/β-catenin-mediated cell metastasis and proliferation. More important, T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors, which are crucial downstream molecules of the Wnt/β-catenin signaling pathway was verified as a valid transcription factor of miR-452's promoter. Our findings first demonstrate that miR-452-GSK3β-LEF1/TCF4 positive feedback loop induce CRC proliferation and migration. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 26 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 4 | 15% |
Other | 3 | 12% |
Lecturer | 2 | 8% |
Student > Bachelor | 2 | 8% |
Unspecified | 1 | 4% |
Other | 5 | 19% |
Unknown | 9 | 35% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 5 | 19% |
Medicine and Dentistry | 5 | 19% |
Agricultural and Biological Sciences | 2 | 8% |
Nursing and Health Professions | 2 | 8% |
Arts and Humanities | 1 | 4% |
Other | 2 | 8% |
Unknown | 9 | 35% |