Abstract
BackgroundGastric 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.MethodThe 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.ResultsIGF2BP3 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.ConclusionWe 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.
Highlights
Gastric cancer (GC) is one of the frequent causes of cancer-related death in eastern Asian population
We found Insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) might be regulated by miR-34a, which was listed in the relative top rank. microRNAs has been thought to be new regulators of gene expression through binding to the 3' untranslated regions (UTRs) of the targeted mRNAs [14], and degrade or translationally inhibit those targeted mRNAs
Based on The Cancer Genome Atlas (TCGA) cohort, IGF2BP3 showed significantly up-regulated in both intestinal- and diffuse- types of GC when compared with normal control (P < 0.001, Fig. 1e)
Summary
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. Its incidence ranks the 4th in men and 5th in women while it causes the 3rd cancer-related death for men and 5th for women [1]. Zhou et al Molecular Cancer (2017) 16:77 microarray analysis in nine GC cell lines, we found IGF2BP3 (Insulin-like growth factor-2 mRNA-binding protein 3) listing in the No. rank of the up-regulated genes. IGF2BP3 has soon been explicated to be a mainly over-expressed member among the family in various tumor types, such as squamous cell carcinoma [7], lung cancer [8], melanoma [9], colon cancer [10], liver cancer [11]. Knowledge of its function and regulation in GC is still quite limited
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
