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Molecular Cancer
Published in: Molecular Cancer 1/2016

Open Access 01-12-2016 | Research

miR-508-3p concordantly silences NFKB1 and RELA to inactivate canonical NF-κB signaling in gastric carcinogenesis

Authors: Tingting Huang, Wei Kang, Bin Zhang, Feng Wu, Yujuan Dong, Joanna H. M. Tong, Weiqin Yang, Yuhang Zhou, Li Zhang, Alfred S. L. Cheng, Jun Yu, Ka Fai To

Published in: Molecular Cancer | Issue 1/2016

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Abstract

Background

NF-κB signaling pathway plays an important role in gastric carcinogenesis. The basic expression and functional role of NFKB1 and RELA (components of canonical NF-κB pathway) in gastric cancer (GC) have not been well elucidated. In this study, the role of NFKB1 and RELA in gastric tumorigenesis will be investigated and their regulation by microRNAs (miRNAs) will be deeply explored.

Methods

The mRNA and protein expression of NFKB1 and RELA were investigated by qRT-PCR and Western blot in GC cell lines and primary tumors. The functional roles of NFKB1 and RELA in GC were demonstrated by MTT proliferation assay, monolayer colony formation, cell invasion and migration, cell cycle analysis and in vivo study through siRNA mediated knockdown. Identification of NFKB1 as a direct target of tumor suppressor miRNA miR-508-3p was achieved by expression regulation assays together with dual luciferase activity experiments.

Results

NFKB1 and RELA were up-regulated in GC cell lines and primary tumors compared with normal gastric epithelium cells and their upregulation correlation with poor survival in GC. siRNA mediated knockdown of NFKB1 or RELA exhibited anti-oncogenic effect both in vitro and in vivo. NFKB1 was further revealed to be a direct target of miR-508-3p in gastric tumorigenesis and their expression showed negative correlation in primary GC samples. miR-508-3p was down-regulated in GC cells compared with normal gastric epithelium samples and its ectopic expression in GC cell lines also exerts tumor suppressor function. NFKB1 re-expression was found to partly abolish the tumor-suppressive effect of miR-508-3p in GC.

Conclusion

All these findings supports that canonical NF-κB signaling pathway is activated in GC at least by the inactivation of miR-508-3p and this might have therapeutic potential in GC treatment.
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Metadata
Title
miR-508-3p concordantly silences NFKB1 and RELA to inactivate canonical NF-κB signaling in gastric carcinogenesis
Authors
Tingting Huang
Wei Kang
Bin Zhang
Feng Wu
Yujuan Dong
Joanna H. M. Tong
Weiqin Yang
Yuhang Zhou
Li Zhang
Alfred S. L. Cheng
Jun Yu
Ka Fai To
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2016
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-016-0493-7

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