Evidence map›Paper›PMID 40476478›Full record

ArticleCancer medicine2025

Hepatitis B Virus X Protein Upregulates SREBP2 to Modulate Autophagy in Hepatocellular Carcinoma.

Qiuyan Lin, Yongxu Lin, Yongzhu Huang, Mingrong Wang, Xiaoxia Xie, Weiqi Cai, Qilan Guo, Pingying Jiang, Yuanlin Qi, Dan Li

Abstract read
In one paragraph

Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

10 authors.

Qiuyan LinDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.ORCID https://orcid.org/0000-0002-4508-8726
Yongxu LinDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Yongzhu HuangDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Mingrong WangDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Xiaoxia XieDepartment of Infection, Fujian Provincial Hospital, Fuzhou, Fujian, China.
Weiqi CaiDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Qilan GuoDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Pingying JiangDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Yuanlin QiSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.ORCID https://orcid.org/0000-0002-5253-9732
Dan LiDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.ORCID https://orcid.org/0000-0003-1975-3785

Funding

National Natural Science Foundation Project 81300321the Fujian Provincial Health Technology Project 2020QNB019the Fujian Provincial Natural Science Foundation of China 2020J011025the Fujian Provincial Natural Science Foundation of China 2022J01730the Fujian Provincial Natural Science Foundation of China 2023J01671the Innovation of Science and Technology 2021Y9064
6 · The paper itself

Abstract

backgroundThe interaction between Hepatitis B virus X protein (HBx) and sterol regulatory element binding protein 2 (SREBP2) in modulating autophagy to influence inflammation and tumorigenesis is not fully understood. This research seeks to clarify the regulatory role of HBx in hepatocyte autophagy through SREBP2.

methodsThe study employed TCGA and GEO databases to investigate the expression of SREBF2 and autophagy-related proteins in liver cancer. Various experimental techniques, including dual-luciferase reporter assays, immunohistochemistry, Western blotting, immunofluorescence, GFP-mRFP-LC3 puncta analysis, transmission electron microscopy, and Fillipin III staining, were conducted on HBV-associated liver cancer tissues, HBV transgenic mice, and several liver cancer cell lines to assess the levels of HBx, SREBP2, autophagy, and cholesterol, respectively, as well as to explore potential associations between these factors.

resultsBioinformatics analysis suggested up-regulation of SREBP2 and autophagy-associated genes in HBV-associated liver cancer. Elevated levels of cholesterol, SREBP2, and autophagy flux were detected in HBV-associated liver cancer tissues as compared to adjacent tissues. HBV transgenic mice had higher cholesterol, SREBP2, and autophagy levels than wild-type mice. HBx activated the SREBP2 promoter to enhance its transcription and nuclear translocation. HBx knockdown down-regulated SREBP2 expression and nuclear translocation levels in HepG2.2.15-siHBx cells. HepG2.2.15 and HepG2-HBx showed more autolysosomes than HepG2 cells; furthermore, HepG2.2.15-siHBx cells had fewer autolysosomes than HepG2.2.15 cells.

conclusionsThis research highlights that HBx upregulates SREBP2 and increases autophagic flux, accompanied by changes in cholesterol metabolism, which offers an additional theoretical foundation to elucidate that chronic HBV infection causes abnormal lipid metabolism and induces tumorigenesis.

Indexed as

AutophagyCarcinoma, HepatocellularLiver NeoplasmsSterol Regulatory Element Binding Protein 2Trans-ActivatorsViral Regulatory and Accessory ProteinsAnimalsCell Line, TumorCholesterolGene Expression Regulation, NeoplasticHepatitis B virusHep G2 CellsHumansMiceMice, TransgenicUp-RegulationCholesterolhepatitis B virus X proteinSREBF2 protein, humanSterol Regulatory Element Binding Protein 2Trans-ActivatorsViral Regulatory and Accessory ProteinsautophagycholesterolHepatitis B virus X proteinhepatocellular carcinomasterol regulatory element binding protein 2

Identifiers

PMID40476478
PMCPMC12142432

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.