Evidence map›Paper›PMID 42713672›Full record

ArticleCancer science2026

The DNA/RNA Helicase SETX Maintains R-Loop Homeostasis to Promote Chemoresistance in Ovarian Cancer.

Zi-Wei Hu, Tu-Nan Xu, Zi-Ying Wang, Xin Zheng, Duan-Yong Feng, Xiao-Min Wang, Er-Suo Jin, Ming Ren, Xiao-Min Yang, Xian-Chao Zhang and 4 more

Abstract read
In one paragraph

Article in Cancer science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Zi-Wei HuDepartment of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.ORCID https://orcid.org/0000-0002-6650-555X
Tu-Nan XuKey Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Zi-Ying WangDepartment of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.
Xin ZhengDepartment of Pathology, First Affiliated Hospital of Jiaxing University/The First Hospital of Jiaxing, Zhejiang, China.
Duan-Yong FengCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Zhejiang, China.
Xiao-Min WangDepartment of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.ORCID https://orcid.org/0000-0001-7128-8097
Er-Suo JinDepartment of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.
Ming RenDepartment of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.
Xiao-Min YangDepartment of Anesthesiology, Jiaxing Hospital of Traditional Chinese Medicine, Zhejiang, China.
Xian-Chao ZhangInstitute of Information Network and Artificial Intelligence, Jiaxing University, Jiaxing, China.
Xuan CheDepartment of Anesthesiology, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, China.
Wei-Wei PanDepartment of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.
Zha-Jun ZhanKey Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Shu-Qun ChengDepartment of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.ORCID https://orcid.org/0000-0001-6760-7470

Funding

Jiaxing talent pioneer innovation team 6.2021National Natural Science Foundation of China 31871402Natural Science Foundation of Zhejiang Province LMS26H160016Natural Science Foundation of Zhejiang Province LY21H160047Science and Technology Bureau Project of Jiaxing 2024AD10007Science and Technology Bureau Project of Jiaxing 2025CGZ021
6 · The paper itself

Abstract

Ovarian cancer is a lethal malignancy that frequently develops resistance to platinum-based chemotherapies. Elucidating the genes that regulate DNA damage repair could lead to more effective treatments for ovarian cancer. Senataxin (SETX), an RNA-DNA helicase, maintains R-loop homeostasis to ensure replication fork progression, and its deficiency is linked to neurodegenerative diseases. However, its clinical relevance to solid tumors is not understood. We aimed to investigate the clinical significance and functional role of SETX in ovarian cancer progression and chemotherapy resistance. SETX expression was analyzed in ovarian cancer tissues, followed by CRISPR-Cas9-mediated knockout, mechanistic analyses, and RNASEH1 rescue experiments to investigate its role in ovarian cancer progression and chemoresistance. SETX was significantly overexpressed in ovarian tumors, and its high expression was correlated with cisplatin resistance and poor patient survival. SETX depletion significantly impaired tumor cell proliferation and invasion and sensitized cells to cisplatin-induced apoptosis. Mechanistically, SETX deficiency triggered pathological R-loop accumulation, which was accompanied by replication stress, DNA double-strand breaks, and activation of DNA damage response. RNA-seq analysis also revealed splicing alterations and U2AF1 interaction. Critically, R-loop degradation induced by RNASEH1 overexpression rescued the DNA damage phenotype and growth defects induced by SETX loss. These findings reveal a dual oncogenic role for SETX. Maintaining R-loop homeostasis supports malignant progression while conferring chemotherapy resistance. Therefore, SETX represents a promising therapeutic target, as its inhibition simultaneously suppresses tumor growth and overcomes chemotherapy resistance in ovarian cancer.

Indexed as

chemoresistanceDNA damage responseovarian cancerR‐loopsSenataxin (SETX)

Identifiers

PMID42713672
PMCPMC13555362

What OpenQuestion holds

Textmetadata
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.