Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Hepatitis B Virus Core Protein Mediates the Upregulation of C5α Receptor 1 via NF-κB Pathway to Facilitate the Growth and Migration of Hepatoma Cells: Fanyun Kong, Yukai Tao, Dongchen Yuan, Ning Zhang, Qi Li, Tong Yu, Xiaoying Yang, Delong Kong, Xiaohui Ding, Xiangye Liu, Hongjuan You, Kuiyang Zheng, Renxian Tang; Cancer Res Treat. 2021;53(2):506-527. Published online November 16, 2020; DOI: https://doi.org/10.4143/crt.2020.397

Purpose
C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells.
Materials and Methods
The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured.
Results
C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1.
Conclusion
We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.

Citations

Citations to this article as recorded by

Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB
Peili Hou, Hongchao Zhu, Fengyun Chu, Yan Gao, Xiaonan Sun, Fuzhen Zhang, Xiaomeng Wang, Yueyue Feng, Xingyu Li, Yu Liu, Jun Wang, Xiaoyun Wang, Daniel Chang He, Hongmei Wang, Hongbin He
Nature Communications.2025;[Epub] CrossRef
HBV core protein enhances WDR46 stabilization to upregulate NUSAP1 and promote HCC progression
Fanyun Kong, Ensi Bao, Yujie Zhong, Yuxin Wang, Ruyu Liu, Huanyang Zhang, Lu Yang, Rong Jiang, Xuanke Liu, Chen Li, Xiangye Liu, Xiucheng Pan, Kuiyang Zheng, Hongjuan You, Renxian Tang
Hepatology Communications.2025;[Epub] CrossRef
Transcriptional regulation of tumor suppressor gene RASSF1A by HBx
Yanhong Kang, Wei Li, Junfeng Wei, Lin Yang, Yi Kang
Molecular and Cellular Probes.2025; 82: 102034. CrossRef
Hepatitis B virus core protein promotes liver cancer progression by stabilizing CANX and suppressing IRF7 transcription
Hong-juan You, Huan-yang Zhang, Yu-jie Zhong, Ru-yu Liu, Lu Yang, Rong Jiang, Yu-xin Wang, En-si Bao, Xiang-ye Liu, Chen Li, Xiu-cheng Pan, Xu-feng Huang, Kui-yang Zheng, Ren-xian Tang, Fan-yun Kong
Acta Pharmacologica Sinica.2025; 46(11): 3036. CrossRef
Effects of interleukin‑6 genetic variation on hepatitis B virus infection and susceptibility to hepatocellular carcinoma: A systematic review and meta‑analysis
Bibin Antony, Karthikeyan Murugesan, Anjuna Radhakrishnan, Yupa Min, Gowtham Subbaraj
World Academy of Sciences Journal.2025; 7(4): 1. CrossRef
Understanding the role of C5a/C5aR1-mediated complement activation pathway in tumor progression and therapy resistance
Lemei Zheng, Jianxia Wei, Mengna Li, Changning Xue, Qingqing Wei, Zubing Wu, Xiaolong Li, Ting Zeng, Huizhen Xin, Wei Xiong, Hongyu Deng, Ming Zhou
Science China Life Sciences.2025;[Epub] CrossRef
Bioinformatics analysis reveals C5AR1’s impact on thyroid cancer development via immune infiltration
Yueyao Sun, Lei Xu, Xiaowen Ma, Haobo Wang, Zihao Li, Ji Feng, Tongtong Ji, Qi Wang, Bo Liu, Fangjian Shang
Scientific Reports.2025;[Epub] CrossRef
Hepatitis B virus core protein stabilizes RANGAP1 to upregulate KDM2A and facilitate hepatocarcinogenesis
Hong-Juan You, Li-Hong Ma, Xing Wang, Yu-Xin Wang, Huan-Yang Zhang, En-Si Bao, Yu-Jie Zhong, Xiang-Ye Liu, De-Long Kong, Kui-Yang Zheng, Fan-Yun Kong, Ren-Xian Tang
Cellular Oncology.2024; 47(2): 639. CrossRef
Colchicine-mediated selective autophagic degradation of HBV core proteins inhibits HBV replication and HBV-related hepatocellular carcinoma progression
Hui Zhang, Xiameng Su, Leirong Gu, Ming Tan, Yuting Liu, Kexin Xu, Jihua Ren, Juan Chen, Zhihong Li, Shengtao Cheng
Cell Death Discovery.2024;[Epub] CrossRef
Hepatitis B virus X protein increases LASP1 SUMOylation to stabilize HER2 and facilitate hepatocarcinogenesis
Hongjuan You, Dongchen Yuan, Qi Li, Ning Zhang, Delong Kong, Tong Yu, Xiangye Liu, Xiaomei Liu, Rui Zhou, Fanyun Kong, Kuiyang Zheng, Renxian Tang
International Journal of Biological Macromolecules.2023; 226: 996. CrossRef
PLK3 promotes the proneural–mesenchymal transition in glioblastoma via transcriptional regulation of C5AR1
Shuo Yu, Lin Lv, Yang Li, Qian Ning, Tingting Liu, Tinghua Hu
Molecular Biology Reports.2023; 50(10): 8249. CrossRef
The role of UXT in tumors and prospects for its application in hepatocellular carcinoma
Zhengwang Wang, Shaojian Mo, Pengzhe Han, Lu Liu, Ziang Liu, Xifeng Fu, Yanzhang Tian
Future Oncology.2022; 18(29): 3335. CrossRef
C5aR1 promotes the progression of colorectal cancer by EMT and activating Wnt/β-catenin pathway
Duo Xu, Meirong Li, Longyan Ran, Xiaochen Li, Xingwang Sun, Tao Yin
Clinical and Translational Oncology.2022; 25(2): 440. CrossRef
The Complement System: A Potential Therapeutic Target in Liver Cancer
Meng Yuan, Li Liu, Chenlin Wang, Yan Zhang, Jiandong Zhang
Life.2022; 12(10): 1532. CrossRef
A Pleiotropic Role of the Hepatitis B Virus Core Protein in Hepatocarcinogenesis
Caroline Lefeuvre, Hélène Le Guillou-Guillemette, Alexandra Ducancelle
International Journal of Molecular Sciences.2021; 22(24): 13651. CrossRef

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Factors Influencing Imatinib-Induced Hepatotoxicity: Ji Min Han, Jeong Yee, Yoon Sook Cho, Hye Sun Gwak; Cancer Res Treat. 2020;52(1):181-188. Published online June 26, 2019; DOI: https://doi.org/10.4143/crt.2019.131

Abstract PDF PubReader ePub

Purpose
Although imatinib-induced hepatotoxicity may aggravate the patient’s clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinibinduced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity.
Materials and Methods
We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs.
Results
The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ≤ 400 mg.
Conclusion
The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.

Citations

Citations to this article as recorded by

Interindividual variability in imatinib metabolism in human liver microsomes and primary human hepatocytes: Impact of CYP2C8 and CYP3A phenotypes
Bethany D. Latham, Pegah Montazeri, Raeanne M. Lanphier, Amanda J. Gerringer, Tyler Interrante, Corbin D. Jones, Tristan De Busysscher, John K. Fallon, Klarissa D. Jackson
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Efficient treatment of colon cancer with codelivery of TRAIL and imatinib by liposomes
Rongrong Fu, Rui Chang, Andong Peng, Changshun Feng, Weifan Zhu, Yi Chen, Xue Tian, Rui Wang, Hui Yan, Dianlong Jia, Jun Li
Pharmaceutical Development and Technology.2024; 29(1): 52. CrossRef
The prevalence of hepatic and thyroid toxicity associated with imatinib treatment of chronic myeloid leukaemia: a systematic review
Mansour Tobaiqy, Nawal Helmi, Katie MacLure, Sylvia Saade
International Journal of Clinical Pharmacy.2024; 46(2): 368. CrossRef
Tyrosine kinase inhibitors can activate the NLRP3 inflammasome in myeloid cells through lysosomal damage and cell lysis
Emilia Neuwirt, Giovanni Magnani, Tamara Ćiković, Svenja Wöhrle, Larissa Fischer, Anna Kostina, Stephan Flemming, Nora J. Fischenich, Benedikt S. Saller, Oliver Gorka, Steffen Renner, Claudia Agarinis, Christian N. Parker, Andreas Boettcher, Christopher J
Science Signaling.2023;[Epub] CrossRef
NLRP3 and cancer: Pathogenesis and therapeutic opportunities
Isak W. Tengesdal, Charles A. Dinarello, Carlo Marchetti
Pharmacology & Therapeutics.2023; 251: 108545. CrossRef
Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms
Shubhrat Purwar, Anam Fatima, Himashree Bhattacharyya, Lakshmi Venkata Simhachalam Kutikuppala, Matei-Alexandru Cozma, Bahadar Singh Srichawla, Leah Komer, Khulud Mahmood Nurani, Mihnea-Alexandru Găman
World Journal of Hepatology.2023; 15(9): 1021. CrossRef
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Feng-Ru Huang, Wen-Tong Fang, Zi-Ping Cheng, Ye Shen, Dun-Jian Wang, Yong-Qing Wang, Lu-Ning Sun
Archives of Toxicology.2022; 96(4): 1075. CrossRef
A Risk Scoring System Utilizing Machine Learning Methods for Hepatotoxicity Prediction One Year After the Initiation of Tyrosine Kinase Inhibitors
Ji Min Han, Jeong Yee, Soyeon Cho, Min Kyoung Kim, Jin Young Moon, Dasom Jung, Jung Sun Kim, Hye Sun Gwak
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European Journal of Clinical Pharmacology.2020; 76(8): 1183. CrossRef

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Case Report

Hepatitis B Virus Reactivation in a Surface Antigen-negative and Antibody-positive Patient after Rituximab Plus CHOP Chemotherapy: Eui Bae Kim, Dae Sik Kim, Seh Jong Park, Yong Park, Kyoung Ho Rho, Seok Jin Kim; Cancer Res Treat. 2008;40(1):36-38. Published online March 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.1.36

Abstract PDF PubReader ePub

Rituximab is a monoclonal antibody that targets B-lymphocytes, and it is widely used to treat non-Hodgkin's lymphoma. However, its use has been implicated in HBV reactivation that's related with the immunosuppressive effects of rituximab. Although the majority of reactivations occur in hepatitis B carriers, a few cases of reactivation have been reported in HBsAg negative patients. However, reactivation in an HBsAg negative/HBsAb positive patient after rituximab treatment has never been reported in Korea. We present here an HBsAg-negative/HBsAb-positive 66-year-old female who displayed reactivation following rituximab plus CHOP chemotherapy for diffuse large B-cell lymphoma. While she was negative for HBsAg at diagnosis, her viral status was changed at the time of relapse as follows: HBsAg positive, HBsAb negative, HBeAg positive, HBeAb negative and an HBV DNA level of 1165 pg/ml. Our observation suggests that we should monitor for HBV reactivation during rituximab treatment when prior HBV infection or occult infection is suspected, and even in the HBsAg negative/HBsAb positive cases.

Citations

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