Evidence map›Paper›PMID 40514420›Full record

ArticleActa pharmacologica Sinica2025

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 and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta pharmacologica Sinica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Hong-Juan You *Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Huan-Yang Zhang *Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Yu-Jie ZhongJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Ru-Yu LiuDepartment of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Lu YangJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Rong JiangJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Yu-Xin WangJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
En-Si BaoJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Xiang-Ye LiuJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Chen LiJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Xiu-Cheng PanDepartment of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, China.
Xu-Feng HuangJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Kui-Yang ZhengJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Ren-Xian TangJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China. tangrenxian-t@163.com.
Fan-Yun KongJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China. kong.fanyun@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatitis B virus (HBV) infection is a vital risk factor for the development of liver cancer. HBV core protein (HBC) contributes to the tumorigenesis induced by the virus. How HBC regulates liver cancer progress has not been well elucidated yet. Calnexin (CANX) is a molecular chaperone that benefits the folding and quality control of various proteins. Overexpression of CANX is implicated in the development of various type of cancers. In this study we investigated the clinical association and biological effects of CANX in liver cancer, and the underlying mechanisms. We showed that the expression of CANX was significantly increased in HBV-associated liver cancer, and its upregulation was relevant to the unfavorable survival of patients with the tumor. We demonstrated that CANX facilitated the growth and migration ability of HBC-positive tumor cells in vitro and in vivo. We identified CBL as a novel E3 ligase of CANX with the function of inducing the ubiquitination of CANX to promote its degradation. HBC increased the stabilization CANX protein by disrupting its interaction with CBL. We revealed that IRF7, an interferon regulatory factor, was an important downstream target of CANX. CANX inhibited IRF7 transcription to promote the proliferation and migration of HBC-positive tumor cells in vitro and in vivo. HDAC3, a histone deacetylase with the capacity to interact with IRF7 promoter, participated in CANX-mediated inhibition on IRF7 gene transcription. HBC enhanced the interaction between CANX and HDAC3, facilitated the recruitment of HDAC3 to IRF7 promoter, leading to the decrease of IRF7 transcription. Finally, we conducted a high-throughput virtual screening to screen potential CANX inhibitors in the APExBIO bioactive compound library. We showed that a candidate compound fluzoparib effectively suppressed HBC-positive liver cancer cells in vitro and in vivo. Overall, this study underscores the crucial role of CANX and its regulatory mechanisms in promoting HBC-mediated liver cancer progression and reveals the therapeutic potential of targeting CANX in HBV infection-caused liver cancer.

Indexed as

CalnexinHepatitis B Core AntigensInterferon Regulatory Factor-7Liver NeoplasmsViral Core ProteinsAnimalsCell Line, TumorCell MovementCell ProliferationDisease ProgressionFemaleHepatitis B virusHistone Deacetylase 3Histone DeacetylasesHumansMaleCalnexinCANX protein, humanCanx protein, mouseHepatitis B Core AntigensHistone Deacetylase 3Histone DeacetylasesInterferon Regulatory Factor-7IRF7 protein, humanViral Core ProteinsCANXCBLHDAC3Hepatitis B virus core proteinIRF7liver cancer

Identifiers

PMID40514420
PMCPMC12552665

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.