Evidence map›Paper›PMID 40082405›Full record

ArticleSignal transduction and targeted therapy2025

Enhancer transcription profiling reveals an enhancer RNA-driven ferroptosis and new therapeutic opportunities in prostate cancer.

Sheng Ma, Zixian Wang, Zezhong Xiong, Yue Ge, Meng-Yao Xu, Junbiao Zhang, Yuzheng Peng, Qin Zhang, Jiaxue Sun, Zirui Xi and 11 more

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed.

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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

21 authors.

Sheng Ma *Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Zixian Wang *MOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences & Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai, China.
Zezhong Xiong *Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Yue Ge *Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Meng-Yao XuDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Junbiao ZhangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Yuzheng PengDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Qin ZhangDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland.
Jiaxue SunMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences & Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai, China.
Zirui XiDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Hao PengDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Wenjie XuMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences & Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai, China.
Yanan WangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Le LiDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.ORCID 0000-0002-5142-9742
Chunyu ZhangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Zheng ChaoDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Baojun WangDepartment of Urology, Chinese PLA General Hospital, Beijing, China.
Xu GaoDepartment of Urology, Changhai Hospital, Shanghai, China.
Xu ZhangDepartment of Urology, Chinese PLA General Hospital, Beijing, China. xzhang301@163.com.
Gong-Hong WeiMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences & Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai, China. gonghong_wei@fudan.edu.cn.ORCID 0000-0001-6546-9334
Zhihua WangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China. zhwang_hust@hotmail.com.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82073082National Natural Science Foundation of China (National Science Foundation of China) 82173068National Natural Science Foundation of China (National Science Foundation of China) 82203416National Natural Science Foundation of China (National Science Foundation of China) 82311530050National Natural Science Foundation of China (National Science Foundation of China) 82373333
6 · The paper itself

Abstract

Enhancer RNAs (eRNAs), a subclass of non-coding RNAs transcribed from enhancer regions, have emerged as critical regulators of gene expression; however, their functional roles in prostate cancer remain largely unexplored. In this study, we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues. By incorporating chromatin immunoprecipitation sequencing data, we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways. Among these, lactotransferrin-eRNA (LTFe) was markedly downregulated in prostate cancer tissues, with functional analyses revealing its tumor-suppressive role. Mechanistically, LTFe promotes the transcription of its target gene, lactotransferrin (LTF), by interacting with heterogeneous nuclear ribonucleoprotein F (HNRNPF) and facilitating enhancer-promoter chromatin interactions. Furthermore, we demonstrate that the LTFe-LTF axis facilitates ferroptosis by modulating iron transport. Notably, androgen receptor (AR) signaling disrupts LTFe-associated chromatin looping, leading to ferroptosis resistance. Therapeutically, co- administration of the AR inhibitor enzalutamide and the ferroptosis inducer RSL3 significantly suppressed tumor growth, offering a promising strategy for castration-resistant prostate cancer. Collectively, this study provides novel insights into the mechanistic role of eRNAs in prostate cancer, highlighting the LTFe-LTF axis as a critical epigenetic regulator and potential therapeutic target for improved treatment outcomes.

Indexed as

Enhancer Elements, GeneticFerroptosisProstatic NeoplasmsAnimalsBenzamidesCell Line, TumorEnhancer RNAsGene Expression Regulation, NeoplasticHumansMaleMiceNitrilesPhenylthiohydantoinReceptors, AndrogenAR protein, humanBenzamidesEnhancer RNAsenzalutamideNitrilesPhenylthiohydantoinReceptors, Androgen

Identifiers

PMID40082405
PMCPMC11906896

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.