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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Molecular Cancer 1/2017

IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in gastric carcinogenesis

Zeitschrift:
Molecular Cancer > Ausgabe 1/2017
Autoren:
Yuhang Zhou, Tingting Huang, Ho Lam Siu, Chi Chun Wong, Yujuan Dong, Feng Wu, Bin Zhang, William K. K. Wu, Alfred S. L. Cheng, Jun Yu, Ka Fai To, Wei Kang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12943-017-0647-2) contains supplementary material, which is available to authorized users.

Abstract

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.
Zusatzmaterial
Additional file 1: Table S1. Oligonucleotides used in the luciferase activity experiments. The oligonucleotides were annealed and subcloned into pMIR-REPORT via HindIII and SpeI restriction sites. WT (Wild type), full length of the putative miRNA binding site; Mutation, the binding site was mutated. (DOC 34 kb)
12943_2017_647_MOESM1_ESM.doc
Additional file 2: Table S2. Expression microarray. (XLS 4646 kb)
12943_2017_647_MOESM2_ESM.xls
Additional file 3: Figure S1. The correlation of IGF2BP3 copy number changes with it mRNA expression in primary GC samples (*, P < 0.05; TCGA cohort). (TIF 1399 kb)
12943_2017_647_MOESM3_ESM.tif
Additional file 5: Table S4. Correlation of IGF2BP3 expression in GC with other clinicopathologic features (significant P-value in bold and Italic format). The case number and percentage counted were shown in the table. (DOC 64 kb)
12943_2017_647_MOESM5_ESM.doc
Additional file 6: Table S5. Univariate and multivariate Cox regression analysis of the association between clinicopathologic characteristics and disease specific survival in patients with gastric adenocarcinoma (n = 247, significant P-value in bold and Italic format). (DOC 35 kb)
12943_2017_647_MOESM6_ESM.doc
Additional file 7: Table S6. Statistical results of miR-34a survival curve derived from TCGA (sig, significantly; CI, confident interval). (DOCX 15 kb)
12943_2017_647_MOESM7_ESM.docx
Literatur
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