MicroRNA-500 Sustains Nuclear Factor-κB Activation and Induces Gastric Cancer Cell Proliferation and Resistance to Apoptosis

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Jan 18

PMID 25595906

Citations 24

Authors

Liang Zhang

Ya Ding

Zhongyu Yuan

Junling Liu

Jian Sun

Fangyong Lei

Shu Wu

Su Li

Dongsheng Zhang

Affiliations

Soon will be listed here.

Abstract

Ubiquitin deconjugation of key signalling molecules by deubiquitinases (DUBs) such as cylindromatosis (CYLD), A20, and OTU deubiquitinase 7B (OTUD7B) has emerged as an important regulatory mechanism in the downregulation of NF-κB signalling and homeostasis. However, how these serial negative regulations are simultaneously disrupted to result in constitutive activation of NF-κB signalling in cancers remains puzzling. Here, we report that the miR-500 directly repressed the expression of CYLD, OTUD7B, and the A20 complex component Tax1-binding protein 1 (TAX1BP1), leading to ubiquitin conjugation of receptor-interacting protein 1 (RIP1) and sustained NF-Ä¸B activation. Furthermore, we found that miR-500 promoted gastric cancer cell proliferation, survival, and tumorigenicity. Importantly, miR-500 was upregulated in gastric cancer and was highly correlated with malignant progression and poor survival. Hence, we report the uncovering of a novel mechanism for constitutive NF-κB activation, indicating the potentially pivotal role of miR-500 in the progression of gastric cancer.

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