title: N-Myc-interacting protein (NMI) negatively regulates epithelial-mesenchymal transition by inhibiting the acetylation of NF-κB/p65.
abstract: The epithelial-mesenchymal transition (EMT) plays an essential role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and tumor progression. However, the mechanisms underlying this process are poorly understood. Many signaling pathways, including the NF-κB signaling pathway, trigger EMT during development and differentiation. In the present study, we report that N-Myc interactor (NMI) inhibits EMT progression by suppressing transcriptional activities of NF-κB in human gastric cancer cells. We show that the expression of NMI is significantly reduced in invasive gastric cancer cells and gastric cancer tissues. Overexpression of NMI inhibited cell migration and invasion, and this inhibition was enhanced after TNF-α stimulation. Tumorigenicity assay in nude mice support the notion that NMI inhibits EMT in cancer cells. Mechanistically, NMI promotes the interaction between NF-κB/p65 and histone deacetylases (HDACs) and inhibits the acetylation and transcriptional activity of p65. The expression of p65 rescues NMI-mediated inhibition of EMT and the inhibition of the acetylation of p65 mediated by NMI is HDACs-dependent. Taken together, these findings suggest that NMI can suppress tumor invasion and metastasis by inhibiting NF-κB pathways, providing an alternative mechanism for EMT inhibition in stomach neoplasm.
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, 361004, China; Xiehe Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350001, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, 361004, China; Xiehe Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350001, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, 361004, China.
authors.forename: Weixian
authors.initials: W
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
authors.forename: James Y
authors.initials: JY
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China. Electronic address: zhangsq@xmu.edu.cn.
authors.forename: Si Qing
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, 361004, China; Xiehe Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350001, China. Electronic address: jianchunfh2@sina.com.
authors.forename: Jian-Chun
authors.initials: JC
authors.lastname: Cai
mesh_terms: D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D064593:Heterografts; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034622:RNA Interference; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D056572:Histone Deacetylase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C099927:NMI protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D006655:Histone Deacetylases
keywords: EMT; HDACs; NF-κB; NMI; stomach neoplasm