APOBEC3B and IL-6 form a positive feedback loop in hepatocellular carcinoma cells

被引:18
作者
Li, Shuran [1 ]
Bao, Xueyang [1 ]
Wang, Duowei [1 ]
You, Linjun [1 ]
Li, Xianjing [1 ]
Yang, Hongbao [1 ]
Bian, Jinsong [2 ]
Wang, Yun [1 ]
Yang, Yong [1 ]
机构
[1] China Pharmaceut Univ, Ctr New Drug Safety Evaluat & Res, Jiangsu Key Lab Drug Discovery Metab Dis, State Key Lab Nat Med, Nanjing 211198, Jiangsu, Peoples R China
[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117597, Singapore
基金
中国国家自然科学基金;
关键词
APOBEC3B; interleukin-6; hepatitis; hepatocellular carcinoma; HuR; MESSENGER-RNA; TNF-ALPHA; EXPRESSION; DNA; DEAMINATION; PROGRESSION; STABILITY; PROTEINS; PATTERNS; MUTATION;
D O I
10.1007/s11427-016-9058-6
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma (HCC) and APOBEC3B (A3B) remains unknown. It has been confirmed that interleukin-6 (IL-6) has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3B in HepG2 cells. A3B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3B and IL-6, and thereby promoted the prolonged non-resolving inflammation. Collectively, these findings suggest that A3B is essential for oncogenesis of HCC, and is a potential target for preventive intervention.
引用
收藏
页码:617 / 626
页数:10
相关论文
共 41 条
[11]   Hepatocyte IKKβ/NF-κB Inhibits Tumor Promotion and Progression by Preventing Oxidative Stress-Driven STAT3 Activation [J].
He, Guobin ;
Yu, Guann-Yi ;
Temkin, Vladislav ;
Ogata, Hisanobu ;
Kuntzen, Christian ;
Sakurai, Toshiharu ;
Sieghart, Wolfgang ;
Peck-Radosavljevic, Markus ;
Leffert, Hyam L. ;
Karin, Michael .
CANCER CELL, 2010, 17 (03) :286-297
[12]   APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development [J].
Henderson, Stephen ;
Chakravarthy, Ankur ;
Su, Xiaoping ;
Boshoff, Chris ;
Fenton, Tim Robert .
CELL REPORTS, 2014, 7 (06) :1833-1841
[13]   IL-6 as a keystone cytokine in health and disease [J].
Hunter, Christopher A. ;
Jones, Simon A. .
NATURE IMMUNOLOGY, 2015, 16 (05) :448-457
[14]  
JEMAL A, 2011, CA-CANCER J CLIN, V61, P134, DOI [DOI 10.3322/CAAC.20107, DOI 10.3322/caac.20115]
[15]  
Johnson Christopher, 2012, Transl Gastrointest Cancer, V1, P58
[16]   Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H [J].
Koeck, Josef ;
Blum, Hubert E. .
JOURNAL OF GENERAL VIROLOGY, 2008, 89 :1184-1191
[17]   Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets [J].
Koning, Fransje A. ;
Newman, Edmund N. C. ;
Kim, Eun-Young ;
Kunstman, Kevin J. ;
Wolinsky, Steven M. ;
Malim, Michael H. .
JOURNAL OF VIROLOGY, 2009, 83 (18) :9474-9485
[18]   APOBEC3B and AID Have Similar Nuclear Import Mechanisms [J].
Lackey, Lela ;
Demorest, Zachary L. ;
Land, Allison M. ;
Hultquist, Judd F. ;
Brown, William L. ;
Harris, Reuben S. .
JOURNAL OF MOLECULAR BIOLOGY, 2012, 419 (05) :301-314
[19]   APOBEC3B Upregulation and Genomic Mutation Patterns in Serous Ovarian Carcinoma [J].
Leonard, Brandon ;
Hart, Steven N. ;
Burns, Michael B. ;
Carpenter, Michael A. ;
Temiz, Nuri A. ;
Rathore, Anurag ;
Vogel, Rachel I. ;
Nikas, Jason B. ;
Law, Emily K. ;
Brown, William L. ;
Li, Ying ;
Zhang, Yuji ;
Maurer, Matthew J. ;
Oberg, Ann L. ;
Cunningham, Julie M. ;
Shridhar, Viji ;
Bell, Debra A. ;
April, Craig ;
Bentley, David ;
Bibikova, Marina ;
Cheetham, R. Keira ;
Fan, Jian-Bing ;
Grocock, Russell ;
Humphray, Sean ;
Kingsbury, Zoya ;
Peden, John ;
Chien, Jeremy ;
Swisher, Elizabeth M. ;
Hartmann, Lynn C. ;
Kalli, Kimberly R. ;
Goode, Ellen L. ;
Sicotte, Hugues ;
Kaufmann, Scott H. ;
Harris, Reuben S. .
CANCER RESEARCH, 2013, 73 (24) :7222-7231
[20]   Interleukin-6-stimulated progranulin expression contributes to the malignancy of hepatocellular carcinoma cells by activating mTOR signaling [J].
Liu, Feng ;
Zhang, Wen ;
Yang, Fusheng ;
Feng, Tingting ;
Zhou, Meng ;
Yu, Yuan ;
Yu, Xiuping ;
Zhao, Weiming ;
Yi, Fan ;
Tang, Wei ;
Lu, Yi .
SCIENTIFIC REPORTS, 2016, 6