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Frontiers of Medicine

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Front Med    2013, Vol. 7 Issue (2) : 242-254    https://doi.org/10.1007/s11684-013-0256-4
REVIEW
Inflammation and liver tumorigenesis
Beicheng Sun1(), Michael Karin2()
1. Liver Transplantation Center of the First Affiliated Hospital and Cancer Center, Nanjing Medical University, Nanjing 210029, China; 2. Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology, Cancer Center, UCSD School of Medicine, La Jolla, CA 92093-0723, USA
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Abstract

Inflammation has been considered as one of the hallmarks of cancer, and chronic hepatitis is a major cause of liver cancer. This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research, including cellular interaction, cytokines, microRNA and stem cells. All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma.
Keywords hepatocellular carcinoma      hepatitis      cytokine      stem cell      miRNA     
Corresponding Author(s): Sun Beicheng,Email:sunbc@njmu.edu.cn; Karin Michael,Email:karinoffice@ucsd.edu   
Issue Date: 05 June 2013
 Cite this article:   
Beicheng Sun,Michael Karin. Inflammation and liver tumorigenesis[J]. Front Med, 2013, 7(2): 242-254.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-013-0256-4
https://academic.hep.com.cn/fmd/EN/Y2013/V7/I2/242
Fig.1  In the tumor or inflammation microenvironment of chronic hepatitis HCC, macrophages can be classified into type 1 or 2. Both of these types have a central function in modulating inflammation resolution and tumor promotion through interaction with lymphocyte subsets. Type I macrophages emerge in the very early stage of the tumor, recruiting inflammatory cells which mediate the Th1 and Th17 response and promote hepatic compensatory proliferation by cytokines, such as IL-6 and TNF-α. Type II macrophages emerge in the late stage of the tumor and are in charge of Th2 response by recruiting Th2 cells that contributed to immunosuppression. Aside from macrophages, MDSCs contributed an inmmunosuppressive effect during tumor development by secreting IL-10 and TGF-β. Moreover, angiogenesis can be enhanced in the tumor microenvironment due to the secretion of cytokines such as VEGF oriented from type II macrophages and MDSCs.
StudyDifferentially expressed miRNAs (no./total)Most significantly overexpressed miRNAs in hepatocellular carcinomaMost significantly underexpressed miRNAs in hepatocellular carcinoma
Jiang et al. [98]16/16miR-18, miR-21, miR-33, miR-135a, miR-221, miR-130bmiR-101, miR-139, miR-150, miR-199a, miR-199a*, miR-199b, miR-200b, miR-214, miR-223, miR-301
Kutay et al. [99]26/245miR-101b-2, miR-130, miR-130a, miR-172a-2, miR-219-1, miR-23a, miR-23b, miR-24, miR-328-1, let-7a-2, miR-103-2, miR-106, miR-106a-1, miR-106b-1, miR-130a-1, miR-17, miR-20, miR-20-1, miR-21, miR-21-1, miR-320-2, miR-93, miR-99bmiR-122, miR-123, miR-215
Murakami et al. [100]8/30miR-224, miR-18, miR-p18miR-199a*,miR-199a,miR-200a, miR-125a, miR-195
Li et al. [101]10/10miR-181a, miR-221, miR-222, miR-25, miR-34amiR-101,miR-148a,miR-424,miR-214, miR-29c
Wang et al. [102]22/157miR-224, miR-182, miR-183, miR-96, miR-9*, miR-9, miR-222, miR-216, miR-21, miR-186, miR-301, miR-221, miR-155,miR-182*, miR-137, miR-25, miR-324-5p, miR-151, miR-374miR-214, miR-145, miR-139
Budhu et al. [103]20/20miR-338, miR-219-1, miR-207, miR-185miR-30c-1, miR-1-2, miR-34a, miR-19a, miR-148a, miR-124a-2, miR-9-2, miR-148b, miR-122a, miR-125b-2, miR-194, miR-30a, miR-126, miR-60,702.8m2, miR-30e, let-7g
Gramantieri et al. [104]33/35miR-221let-7a-1, let-7a-2, let-7a-3, let-7b, let-7c, let-7d, let-7e, let-7f-2, let-7g, miR-122a, miR-124a-2, miR-130a, miR-132,miR-136, miR-141, miR-142, miR-143, miR-145, miR-146, miR-150, miR-155(BIC), miR-181a-1, miR-181a-2, miR-181c, miR-195, miR-199a-1-5p, miR-199a-2-5p, miR-199b, miR-200b, miR-214, miR-223, mir-594
Varnholt et al. [105]5/80miR-122, miR-100, miR-10amiR-198 and miR-145
Wong et al. [106]2/2miR-222miR-223
Pineau et al. [107]12/70miR-106b, miR-21, miR-210, miR-221, miR-222, miR-224, miR-34a, miR-425, miR-519a, miR-93, miR-96let-7c
Tab.1  Summary of microRNA expression in hepatocellular carcinoma
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