Overexpression of RIP140 suppresses the malignant potential of hepatocellular carcinoma by inhibiting NF‑κB‑mediated alternative polarization of macrophages.

作者: Ying-Chun Hu , Zhu-Jun Yi , Yun Zhou , Pei-Zhi Li , Zuo-Jin Liu

DOI: 10.3892/OR.2017.5551

关键词: Cell growthApoptosisBiologyOncogenePeripheral blood mononuclear cellRegulation of gene expressionMacrophage polarizationMolecular biologyCell cycleSignal transduction

摘要: Abstract Tumor-associated macrophages (TAMs) and their alternative activation contribute greatly to the development of hepatocellular carcinoma (HCC). Receptor-interacting protein 140 (RIP140) is widely expressed in regulates macrophage-mediated energy metabolism, inflammatory response tumorigenesis. However, whether RIP140 involved TAMs has not been reported. In present study, we determined expression after treatment with HCC-conditioned medium (HCM) for 24 h. We also analyzed effects overexpression on macrophage polarization, invasion apoptosis HepG2 Huh7 cells. Transwell assays were used estimated cell apoptosis. addition, investigated growth H22 cells by subcutaneous injection along BALB/c nude mice. Western blotting qRT-PCR detect protein mRNA associated NF-κB/IL-6 axis TAMs. Immunohistochemical immunofluorescence staining evaluate or F4/80 human HCC samples. The peripheral blood mononuclear was detected western blotting. Kaplan‑Meier survival curve estimation overall patients based found that HCM inhibited fostered macrophages. significantly inhibiting TAMs, suppressed both in vitro in vivo. monocytes lower than healthy people, this result consistent Furthermore, low high be closely correlated shorter time HCC.

参考文章(32)
Yi-Wei Lin, Bomi Lee, Pu-Ste Liu, Li-Na Wei, Receptor-Interacting Protein 140 Orchestrates the Dynamics of Macrophage M1/M2 Polarization Journal of Innate Immunity. ,vol. 8, pp. 97- 107 ,(2016) , 10.1159/000433539
Almin I. Lalani, Carissa R. Moore, Chang Luo, Benjamin Z. Kreider, Yan Liu, Herbert C. Morse, Ping Xie, Myeloid cell TRAF3 regulates immune responses and inhibits inflammation and tumor development in mice Journal of Immunology. ,vol. 194, pp. 334- 348 ,(2015) , 10.4049/JIMMUNOL.1401548
Virginia Hernandez–Gea, Sara Toffanin, Scott L. Friedman, Josep M. Llovet, Role of the Microenvironment in the Pathogenesis and Treatment of Hepatocellular Carcinoma Gastroenterology. ,vol. 144, pp. 512- 527 ,(2013) , 10.1053/J.GASTRO.2013.01.002
Ping-Chih Ho, Yao-Chen Tsui, Xudong Feng, David R Greaves, Li-Na Wei, NF-κB-mediated degradation of the coactivator RIP140 regulates inflammatory responses and contributes to endotoxin tolerance Nature Immunology. ,vol. 13, pp. 379- 386 ,(2012) , 10.1038/NI.2238
Pu-Ste Liu, Yi-Wei Lin, Frank H Burton, Li-Na Wei, M1-M2 balancing act in white adipose tissue browning – a new role for RIP140 Adipocyte. ,vol. 4, pp. 146- 148 ,(2015) , 10.4161/21623945.2014.981428
Shanshan Wan, Ende Zhao, Ilona Kryczek, Linda Vatan, Anna Sadovskaya, Gregory Ludema, Diane M. Simeone, Weiping Zou, Theodore H. Welling, Tumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT3 to Promote Expansion of Human Hepatocellular Carcinoma Stem Cells Gastroenterology. ,vol. 147, pp. 1393- 1404 ,(2014) , 10.1053/J.GASTRO.2014.08.039
Wenchao Zhou, Susan Q. Ke, Zhi Huang, William Flavahan, Xiaoguang Fang, Jeremy Paul, Ling Wu, Andrew E. Sloan, Roger E. McLendon, Xiaoxia Li, Jeremy N. Rich, Shideng Bao, Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth Nature Cell Biology. ,vol. 17, pp. 170- 182 ,(2015) , 10.1038/NCB3090
Xudong Feng, Kelly A. Krogh, Cheng-Ying Wu, Yi-Wei Lin, Hong-Chieh Tsai, Stanley A. Thayer, Li-Na Wei, Receptor-interacting protein 140 attenuates endoplasmic reticulum stress in neurons and protects against cell death Nature Communications. ,vol. 5, pp. 4487- 4487 ,(2014) , 10.1038/NCOMMS5487
Marion Lapierre, Sandrine Bonnet, Caroline Bascoul-Mollevi, Imade Ait-Arsa, Stéphan Jalaguier, Maguy Del Rio, Michela Plateroti, Paul Roepman, Marc Ychou, Julie Pannequin, Frédéric Hollande, Malcolm Parker, Vincent Cavailles, RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis Journal of Clinical Investigation. ,vol. 124, pp. 1899- 1913 ,(2014) , 10.1172/JCI65178
Moniek Heusinkveld, Sjoerd H van der Burg, Identification and manipulation of tumor associated macrophages in human cancers Journal of Translational Medicine. ,vol. 9, pp. 216- 216 ,(2011) , 10.1186/1479-5876-9-216