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 |
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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. |
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ISSN: | 1347-9032 1349-7006 |
DOI: | 10.1111/cas.13338 |