title: NMI promotes hepatocellular carcinoma progression via BDKRB2 and MAPK/ERK pathway.
abstract: Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignant tumors. The involvement of N-myc (and STAT) interactor (NMI) and its possible functional mechanisms in HCC progression still remain to be elucidated. In this study, we found that NMI was overexpressed in metastatic HCC cell lines compared with non-metastatic ones; and the expression levels of NMI in the HCC samples with metastasis were higher than that in the non-metastatic specimens. Furthermore, NMI depletion significantly decreased HCC cell proliferation and invasiveness in vitro, and also inhibited tumor growth and lung metastasis in vivo in nude mice models bearing human HCC. By contrast, NMI stable overexpression can enhance the malignant behaviors obviously. Moreover, we further verified that NMI promotes the expression of BDKRB2 and mediates the activation of MAPK/ERK signaling pathway according to the bidirectional perturbations of NMI expression in vivo or in vitro of HCC. Taken together, NMI is a pro-metastatic molecule and partially responsible for HCC tumor growth and motility. NMI could improve its downstream target BDKRB2 expression to induce ERK1/2 activation, and thereby further evoke malignant progression of HCC.
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Department of Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, Shanghai, China.
authors.forename: Qiong-Zhu
authors.initials: QZ
authors.lastname: Dong
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Department of Systems Biology for Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Cai
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Zhao-Yu
authors.initials: ZY
authors.lastname: Qin
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Cheng-Zhao
authors.initials: CZ
authors.lastname: Lin
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Department of Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, Shanghai, China.
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing, China.
authors.forename: Fu-Chu
authors.initials: FC
authors.lastname: He
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D020935:MAP Kinase Signaling System; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D043782:Receptor, Bradykinin B2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C099927:NMI protein, human; D043782:Receptor, Bradykinin B2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: N-myc (and STAT) interactor (NMI); liver cancer; metastasis