Format

Send to

Choose Destination
Oncotarget. 2015 Feb 10;6(4):2483-95.

MicroRNA-500 sustains nuclear factor-κB activation and induces gastric cancer cell proliferation and resistance to apoptosis.

Author information

1
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Department of Diagnostic Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
2
Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
3
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
4
Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
5
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

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-ĸB 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.

PMID:
25595906
PMCID:
PMC4385865
DOI:
10.18632/oncotarget.2800
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center