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IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in
gastric carcinogenesis
#MMPMID28399871
Zhou Y
; Huang T
; Siu HL
; Wong CC
; Dong Y
; Wu F
; Zhang B
; Wu WK
; Cheng AS
; Yu J
; To KF
; Kang W
Mol Cancer
2017[Apr]; 16
(1
): 77
PMID28399871
show ga
BACKGROUND: Gastric cancer (GC) is one of the frequent causes of cancer-related
death in eastern Asian population. IGF2BP2 lists in the top rank up-regulated
genes in GC, but its functional role is unclear. METHOD: The expression of
IGF2BP3 in GC cell lines and primary samples was examined by qRT-PCR and Western
blot. The biological role of IGF2BP3 was revealed by a series of functional in
vitro studies. Its regulation by microRNAs (miRNAs) was predicted by TargetScan
and confirmed by luciferase assays and rescue experiments. RESULTS: IGF2BP3
ranked the No.1 of the up-regulated genes by expression microarray analysis in GC
cell lines. The expression level of IGF2BP3 was observed in GC tissues comparing
with non-tumorous gastric epitheliums. The up-regulated IGF2BP3 expression was
associated with poor disease specific survival. IGF2BP3 knockdown significantly
inhibited cell proliferation and invasion. Apart from copy number gain, IGF2BP3
has been confirmed to be negatively regulated by tumor-suppressive miRNA, namely
miR-34a. The expression of miR-34a showed negative correlation with IGF2BP3 mRNA
expression in primary GC samples and more importantly, re-overexpression of
IGF2BP3 rescued the inhibitory effect of miR-34a. CONCLUSION: We compressively
revealed the oncogenic role of IGF2BP3 in gastric tumorigenesis and confirmed its
activation is partly due to the silence of miR-34a. Our findings identified
useful prognostic biomarker and provided clinical translational potential.
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