Evidence map›Paper›PMID 41271015›Full record

ArticleVirologica Sinica2025

Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication.

Yanfei Liu, Zi Han, Paul Kaminski, Chengcheng Tao, Xiaoge Li, Mengmeng Liu, Yang Li, Ying Jia, Junfen Xu, Shiyuan Hong

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Virologica Sinica, 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. Article
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.

Yanfei LiuCollege of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
Zi HanCollege of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
Paul KaminskiPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States of America.
Chengcheng TaoCollege of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
Xiaoge LiDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Mengmeng LiuOffice of Research Administration, Chongqing Medical University, Chongqing, 400016, China.
Yang LiCollege of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
Ying JiaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Junfen XuDepartment of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. Electronic address: xjfzu@zju.edu.cn.
Shiyuan HongCollege of Pharmacy, Chongqing Medical University, Chongqing, 400016, China. Electronic address: hongshiyuan@cqmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High-risk human papillomavirus (HPV) replication requires deregulation of host DNA damage response (DDR) and inflammatory pathways. DNA topoisomerase 2β (Top2β) was previously shown to promote HPV replication. We investigated whether its paralog Top2α protein acts similarly to the virus. Elevated levels of Top2α are consistently observed in cervical intraepithelial lesions and the related carcinomas, as well as in HPV-positive cell lines. Silencing Top2α with shRNA severely suppresses HPV genome maintenance and amplification, but in a DDR-independent manner. Instead, Top2α facilitates secretion of interleukin (IL)-6 and IL-8, which are necessary for HPV replication. Mechanistically, this manipulation is regulated by toll-like receptor 4 (TLR4). Top2α binds to the TLR4 promoter to transcriptionally induce TLR4 expression. Blockade of TLR4 signaling by the specific inhibitor TAK-242 significantly reduces the secreted IL-6/IL-8 levels and HPV replication. Overall, our results reveal a novel role of Top2α to shape the inflammatory microenvironment that benefits HPV replication, making it a promising therapeutic target for HPV-associated diseases.

Indexed as

DNA Topoisomerases, Type IIInterleukin-6Interleukin-8PapillomaviridaePapillomavirus InfectionsPoly-ADP-Ribose Binding ProteinsVirus ReplicationFemaleHuman Papillomavirus VirusesHumansSignal TransductionToll-Like Receptor 4Uterine Cervical NeoplasmsCXCL8 protein, humanDNA Topoisomerases, Type IIIL6 protein, humanInterleukin-6Interleukin-8Poly-ADP-Ribose Binding ProteinsTLR4 protein, humanToll-Like Receptor 4TOP2A protein, humanHuman papillomavirus (HPV)IL-6/IL-8 secretionReplicationTLR4Topoisomerase 2α

Identifiers

PMID41271015
PMCPMC12826965

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.