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

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-A¸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.
Mesh Terms:
3' Untranslated Regions, Animals, Apoptosis, Blotting, Western, Cell Line, Tumor, Cell Proliferation, Cells, Cultured, Disease Progression, Endopeptidases, Female, Gene Expression Regulation, Neoplastic, Humans, Intracellular Signaling Peptides and Proteins, Male, Mice, Nude, MicroRNAs, Middle Aged, NF-kappa B, Neoplasm Proteins, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Stomach Neoplasms, Survival Analysis, Transplantation, Heterologous, Tumor Suppressor Proteins
Oncotarget
Date: Feb. 10, 2015
Download Curated Data For This Publication
191187
Switch View:
  • Interactions 4