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

Molecular Cancer
Tingting HuangKafai To

Abstract

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. 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. 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-...Continue Reading

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Citations

May 12, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Alvin Ho-Kwan CheungKa-Fai To
Nov 17, 2019·International Journal of Molecular Sciences·Mohamed Zakaria NassefDaniela Grimm
Jul 11, 2020·Chinese Medical Journal·Si-Ran WuYong-Quan Shi
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Nov 5, 2020·Diagnostics·Fatimat KipkeevaAlexander Karpukhin
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Aug 28, 2021·Biomedicines·Supattra ChaithongyotMichael Naumann

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Methods Mentioned

BETA
flow cytometry
transfection
xenografts
xenograft
electrophoresis
Assay
immunoprecipitation
PCR

Software Mentioned

TargetScan
SPSS
KM plotter

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