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2016 ; 7
(15
): 20260-70
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Reactivation of epigenetically silenced miR-124 reverses the
epithelial-to-mesenchymal transition and inhibits invasion in endometrial cancer
cells via the direct repression of IQGAP1 expression
#MMPMID26934121
Dong P
; Ihira K
; Xiong Y
; Watari H
; Hanley SJ
; Yamada T
; Hosaka M
; Kudo M
; Yue J
; Sakuragi N
Oncotarget
2016[Apr]; 7
(15
): 20260-70
PMID26934121
show ga
Overexpression of IQGAP1 and microRNA (miRNA) dysregulation are frequent in human
tumors, but little is known about the role of IQGAP1 and its relationship to
miRNA in endometrial carcinogenesis. We demonstrate that IQGAP1 activates the
epithelial-mesenchymal transition (EMT) program and that miR-124 directly
represses IQGAP1 expression in endometrial cancer (EC) cells. The overexpression
of IQGAP1 stimulates EMT features and enhances migration, invasion and
proliferation of EC cells, whereas knocking down IQGAP1 expression reverses EMT
and inhibits these malignant properties. Using miRNA microarray profiling, we
identified 29 miRNAs (let-7b, let-7f, miR-10b, miR-15b, miR-23a, miR-24, miR-25,
miR-27a, miR-29b, miR-30a-5p, miR-34a, miR-124, miR-127, miR-130b, miR-148a,
miR-155, miR-191*, miR-194, miR-224, miR-362, miR-409-3p, miR-422b, miR-424,
miR-453, miR-497, miR-518d, miR-518f*, miR-526a and miR-656) that are
significantly down-regulated in an in vitro-selected highly invasive derivative
cell line (HEC-50-HI) relative to the parental HEC-50 cells. We further
identified miR-124 as a direct regulator of IQGAP1 in EC cells. Enforced
expression of miR-124 suppresses EC cell invasion and proliferation. The
expression of IQGAP1 mRNA was significantly elevated in EC tissues, while the
expression of miR-124 was decreased. The downregulation of miR-124 correlates
with a poor survival outcome for patients with EC. Treating EC cells with the
demethylating agent 5-aza-2'-deoxycytidine increased miR-124 expression and
down-regulated IQGAP1 levels. Our data suggest that IQGAP1 promotes EMT,
migration and invasion of EC cells. MiR-124, a novel tumor suppressor miRNA that
is epigenetically silenced in EC, can reverse EMT and the invasive properties, by
attenuating the expression of the IQGAP1 oncogene.