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.

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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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Plasma Macrophage Migration Inhibitory Factor and CCL3 as Potential Biomarkers for Distinguishing Patients with Nasopharyngeal Carcinoma from High-Risk Individuals Who Have Positive Epstein-Barr Virus Capsid Antigen-Specific IgA: Ning Xue, Jian-Hua Lin, Shan Xing, Dan Liu, Shi-Bing Li, Yan-Zhen Lai, Xue-Ping Wang, Min-Jie Mao, Qian Zhong, Mu-Sheng Zeng, Wan-Li Liu; Cancer Res Treat. 2019;51(1):378-390. Published online May 29, 2018; DOI: https://doi.org/10.4143/crt.2018.070

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to identify novel plasma biomarkers for distinguishing nasopharyngeal carcinoma (NPC) patients from healthy individuals who have positive Epstein-Barr virus (EBV) viral capsid antigen (VCA-IgA).
Materials and Methods
One hundred seventy-four plasma cytokines were analyzed by a Cytokine Array in eight healthy individuals with positive EBV VCA-IgA and eight patients with NPC. Real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry were employed to detect the expression levels of macrophage migration inhibitory factor (MIF) and CC chemokine ligand 3 (CCL3) in NPC cell lines and tumor tissues. Plasma MIF and CCL3 were measured by ELISA in 138 NPC patients, 127 EBV VCA-IgA negative (VN) and 100 EBV VCA-IgA positive healthy donors (VP). Plasma EBV VCA-IgA was determined by immunoenzymatic techniques.
Results
Thirty-four of the 174 cytokines varied significantly between the VP and NPC group. Plasma MIF and CCL3 were significantly elevated in NPC patients compared with VN and VP. Combination of MIF and CCL3 could be used for the differential diagnosis of NPC from VN cohort (area under the curve [AUC], 0.913; sensitivity, 90.00%; specificity, 80.30%), and combination of MIF, CCL3, and VCA-IgA could be used for the differential diagnosis of NPC from VP cohort (AUC, 0.920; sensitivity, 90.00%; specificity, 84.00%), from (VN+VP) cohort (AUC, 0.961; sensitivity, 90.00%; specificity, 92.00%). Overexpressions of MIF and CCL3 were observed in NPC plasma, NPC cell lines and NPC tissues.
Conclusion
Plasma MIF, CCL3, and VCA-IgA combination significantly improves the diagnostic specificity of NPC in high-risk individuals.

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Roles of Macrophage Migration Inhibitory Factor (MIF) Signaling Pathway in Oncovirus Infection and Virus-Associated Cancers
Jiaojiao Fan, Victor Ryu, Zhiqiang Qin, Lu Dai
Viruses.2025; 17(12): 1582. CrossRef
Nasopharyngeal carcinoma-associated inflammatory cytokines: ongoing biomarkers
Chuwen Liang, Jun Kan, Jingli Wang, Wei Lu, Xiaoyan Mo, Bei Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Genetic Variants of the MIF Gene and Susceptibility of Rectal Cancer
Dongyu Chuo, Dapeng Lin, Mingdi Yin, Yuze Chen
Pharmacogenomics and Personalized Medicine.2021; Volume 14: 55. CrossRef
microRNA-451 (miR-451) Regulates the Apoptosis of Non-Small Cell Lung Cancer Cells by Targeting Macrophage Migration Promoting Factors
Caihong Wei, Dan Guo, Huayun Pu
Journal of Biomaterials and Tissue Engineering.2021; 11(7): 1388. CrossRef

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MicroRNA-373 Inhibits Cell Proliferation and Invasion via Targeting BRF2 in Human Non-small Cell Lung Cancer A549 Cell Line: Lei Wang, Junfeng Qu, Li Zhou, Fei Liao, Ju Wang; Cancer Res Treat. 2018;50(3):936-949. Published online October 12, 2017; DOI: https://doi.org/10.4143/crt.2017.302

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the biological role and mechanism of miR-373 targeting of TFIIB-related factor 2 (BRF2) in the regulation of non-small cell lung cancer (NSCLC) cells. MaterialsandMethods miRNA microarray chip analysis of four paired NSCLC and adjacent non-tumor tissues was performed. Quantitative real-time polymerase chain reaction (qRT-PCR) andwestern blotting were used to detect the expression levels of miR-373 and BRF2 in NSCLC tissues and cell lines. The dual-luciferase reporter method was performed to determine if BRF2 is a target of miR-373. MTT, wound-healing, Transwell, and flow cytometric assays were conducted to examine the proliferation, migration, invasion, and cell cycle progression of NSCLC A549 cells, respectively; western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)–related proteins.
Results
The miRNA microarray chip analysis demonstrated that miR-373 was down-regulated in NSCLC tissues, and this result was confirmed by qRT-PCR. Additionally, miR-373 was confirmed to target BRF2. Moreover, miR-373 expression was inversely correlated with BRF2 expression in NSCLC tissues and cell lines; both miR-373 down-regulation and BRF2 up-regulation were strongly associated with the clinicopathological features and prognosis of NSCLC patients. In vitro, overexpression of miR-373 markedly inhibited cell proliferation, migration, and invasion; up-regulated the expression of E-cadherin; and down-regulated the expression of N-cadherin and Snail in A549 cell. Knockdown BRF2 by siRNA resulted in effects similar to those caused by overexpression of miR-373.
Conclusion
MiR-373 is decreased in NSCLC, and overexpression of miR-373 can suppress cell EMT, and inhibit the proliferation, migration, and invasion of NSCLC A549 cells by targeting BRF2.

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Xingwei Wu, Zhenguo Wu, Zehang Xie, Haoyu Huang, Yingying Wang, Kun Lv, Hui Yang, Xiaocen Liu
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Yanping Cheng, Sheng Yang, Bo Shen, Yan Zhang, Xiaomei Zhang, Tong Liu, Siyi Xu, Jing Sui, Lihong Yin, Yuepu Pu, Geyu Liang
Journal of Cellular Biochemistry.2020; 121(4): 2889. CrossRef
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Yu Tian, Cong Wang, Ming Lu
Surgery Today.2019; 49(2): 158. CrossRef
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Jing Zheng, Tingting Xu, Feng Chen, Ying Zhang
Pathology & Oncology Research.2019; 25(3): 1181. CrossRef
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Shigehiro Ito, Yasuhiro Miki, Ryoko Saito, Chihiro Inoue, Yoshinori Okada, Hironobu Sasano
Pathology - Research and Practice.2019; 215(8): 152463. CrossRef
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Localization of Urokinase Type Plaminogen Activator Receptor on Tumor Cells by Tmmunohistochemistry: Hye Won Park, Yoon Hoh Kook, Sung Bae Choi, ng Yong Cha; J Korean Cancer Assoc. 1996;28(1):159-168.

Abstract PDF: Urokinase type plasminogen activator(uPA) plays important role in invasion and metastasis of cancer. Its actions are activated and amplified by a specific cell-surface receptor (urokinase type plasminogen activator receptor: uPAR). The present study was undertaken to determine the importance of the uPAR for migration and invasion of cancer cells through immunohistochemical localization of uPAR. HEp3 cells were cultured in monolayer and suspended, then they were stained by immunofluorescence, APAAP(alkaline phosphatase anti-alkaline phosphatase) and immunoperoxidase method. The receptor(uPAR) was found to be located at cellular contact sites. In suspension uPAR staining of HEp3 cells showed focal distribution. In vivo model of invasion, the uPAR was localized on leading edge of tumor of cholioallatoic membrane(CAM) inoculated with HEp3 cells. This suggests that uPAR might play crucial role in migration and invasion of cancer cells through mediating proteolysis at cellular contact sites especially in leading edge of the tumor.

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