title: Targeting MUC1 and JNK by RNA interference and inhibitor inhibit the development of hepatocellular carcinoma.
abstract: Mucin 1 (MUC1), as an oncogene, is overexpressed in hepatocellular carcinoma (HCC) cells and promotes the progression and tumorigenesis of HCC through JNK/TGF-β signaling pathway. In the present study, RNA interference (RNAi) and JNK inhibitor SP600125, which target MUC1 and/or JNK, were used to treat HCC cells in vitro, and the results showed that both silencing the expression of MUC1 and blocking the activity of JNK inhibited the proliferation of HCC cells. In addition, MUC1-stable-knockdown and SP600125 significantly inhibited the growth of tumors in the subcutaneous transplant tumor models that established in BALB/c nude mice rather than MUC1 or JNK siRNAs transiently transfection. Furthermore, the results from immunohistochemical staining assays showed that the inhibitory effects of MUC1 gene silencing and SP600125 on the proliferation of HCC cells in vivo were through the JNK/TGF-β signaling pathway. These results indicate that MUC1 and JNK are attractive targets for HCC therapy and may provide new therapeutic strategies for the treatment of HCC.
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Ni
authors.affiliation: Department of Urology, The First Hospital of Jilin University, Changchun, China.
authors.forename: Ke-Bang
authors.initials: KB
authors.lastname: Hu
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhai
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jie
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Zhang
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Jiang
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Yuan
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Tai
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018396:Mucin-1 / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000873:Anthracenes; C060192:MUC1 protein, human; D018396:Mucin-1; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases
keywords: RNAi; TGF-β; c-Jun N-terminal kinase; hepatocellular carcinoma; mucin 1