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The SOX17/miR-371-5p/SOX2 axis inhibits EMT, stem cell properties and metastasis
in colorectal cancer
#MMPMID25868860
Li Y
; Lv Z
; He G
; Wang J
; Zhang X
; Lu G
; Ren X
; Wang F
; Zhu X
; Ding Y
; Liao W
; Ding Y
; Liang L
Oncotarget
2015[Apr]; 6
(11
): 9099-112
PMID25868860
show ga
Cancer stem cells (CSCs) and EMT-type cells, which share molecular
characteristics with CSCs, have been believed to play critical roles in tumor
metastasis. Although much progress has been garnered in elucidating the molecular
pathways that trigger EMT, stemness and metastasis, a number of key mechanistic
gaps remain elusive. In the study, miR-371-5p was obviously down-regulated in
primary CRC tissues compared with matched adjacent normal mucosa and correlated
significantly with differentiation, tumor size, lymphatic and liver metastases.
MiR-371-5p could attenuate proliferation, invasion in vitro and metastasis in
vivo in CRC cells. It also suppressed EMT by regulating Wnt/?-catenin signaling
and strongly decreased the CRC stemness phenotypes. Moreover, demethylation of
SOX17 induced miR-371-5p expression and consequently suppressed its direct target
SOX2 in CRC cells. MiR-371-5p was necessary for SOX17 mediated cancer-related
traits and SOX2 was a functional target of miR-371-5p. A positive relationship
between SOX17 and miR-371-5p expression and a negative one between miR-371-5p and
SOX2 expression were observed in CRC cell lines and tissues. In conclusion, we
identified miR-371-5p as an important "oncosuppressor" in CRC progression and
elucidated a novel mechanism of the SOX17/miR-371-5p/SOX2 axis in the regulation
of EMT, stemness and metastasis, which may be a potential therapeutic target.
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