micro RNA ‐219‐5p inhibits epithelial‐mesenchymal transition and metastasis of colorectal cancer by targeting lymphoid enhancer‐binding factor 1

Aberrant expression of micro RNA s (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. micro RNA ‐219‐5p (miR‐219‐5p) has been reported to be abnormally expressed in some types of human tumors. However, the mechanism between miR‐219‐5p and colorectal cancer (...

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Veröffentlicht in:Cancer science 2017-10, Vol.108 (10), p.1985-1995
Hauptverfasser: Huang, Lan‐xuan, Hu, Chun‐yan, Jing, Li, Wang, Min‐cong, Xu, Meng, Wang, Jing, Wang, Yu, Nan, Ke‐jun, Wang, Shu‐hong
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Sprache:eng
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Zusammenfassung:Aberrant expression of micro RNA s (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. micro RNA ‐219‐5p (miR‐219‐5p) has been reported to be abnormally expressed in some types of human tumors. However, the mechanism between miR‐219‐5p and colorectal cancer ( CRC ) metastasis remains unclear. In the present study, miR‐219‐5p was found to be downregulated in CRC tissue compared with matched normal tissue. Through luciferase reporter assay, we demonstrated lymphoid enhancer‐binding factor 1 ( LEF 1) as a direct target of miR‐219‐5p. Overexpression of miR‐219‐5p could inhibit motility, migration and invasion of CRC cells, and inhibit epithelial‐mesenchymal transition ( EMT ). Furthermore, silencing LEF 1 phenocopied this metastasis‐suppressive function. The recovery experiment showed that re‐expression of LEF 1 rescued this suppressive effect on tumor metastasis and reversed the expression of EMT markers caused by miR‐219‐5p. Additionally, we demonstrated that miR‐219‐5p exerted this tumor‐suppressive function by blocking activation of the AKT and ERK pathways. Finally, a nude mice experiment showed that miR‐219‐5p reduced the lung metastasis ability of CRC cells. Taken together, our findings indicate that miR‐219‐5p inhibits metastasis and EMT of CRC by targeting LEF 1 and suppressing the AKT and ERK pathways, which may provide a new antitumor strategy to delay CRC metastasis.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.13338