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Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer
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Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer
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Journal Article
Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer
2015
Overview
Background:
Analysis of a microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that clustered miRNAs
microRNA
(
miR
)
-451a
,
miR-144-3p
, and
miR-144-5p
were significantly downregulated in BC tissues. We hypothesised that these miRNAs function as tumour suppressors in BC. The aim of this study was to investigate the functional roles of these miRNAs and their modulation of cancer networks in BC cells.
Methods:
The functional studies of BC cells were performed using transfection of mature miRNAs. Genome-wide gene expression analysis,
in silico
analysis, and dual-luciferase reporter assays were applied to identify miRNA targets. The association between
miR-144-5p
levels and expression of the target genes was determined, and overall patient survival as a function of target gene expression was estimated by the Kaplan–Meier method.
Results:
Gain-of-function studies showed that
miR-144-5p
significantly inhibited cell proliferation by BC cells. Four cell cycle-related genes (
CCNE1
,
CCNE2
,
CDC25A
, and
PKMYT1
) were identified as direct targets of
miR-144-5p
. The patients with high
CCNE1
or
CCNE2
expression had lower overall survival probabilities than those with low expression (
P
=0.025 and
P
=0.032).
Conclusion:
miR-144-5p
functions as tumour suppressor in BC cells.
CCNE1
and
CCNE2
were directly regulated by
miR-144-5p
and might be good prognostic markers for survival of BC patients.
Publisher
Nature Publishing Group UK,Nature Publishing Group
