title: MicroRNA-500 sustains nuclear factor-κB activation and induces gastric cancer cell proliferation and resistance to apoptosis.
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.
authors.affiliation: 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.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Liu
authors.affiliation: Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Fangyong
authors.initials: F
authors.lastname: Lei
authors.affiliation: Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.affiliation: Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D000074749:Deubiquitinating Enzyme CYLD; D018450:Disease Progression; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; C547054:MIRN500 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D009363:Neoplasm Proteins; C120635:TAX1BP1 protein, human; D025521:Tumor Suppressor Proteins; D010450:Endopeptidases; C476458:OTUD7B protein, human; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD