Evidence map›Paper›PMID 41214698›Full record

ArticleCell communication and signaling : CCS2025

Epigenetic regulation of NR5A2 influences colorectal cancer cell stemness via a stemness-related transcription factor NANOG.

Jia Liu, Li Li, Liang Zhang, Wenpeng Wang, Lei Zheng, Dalu Kong, Jiefu Wang, Yang Zhan

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Jia Liu *Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, China. liujia6771@tjmuch.com.
Li Li *Department of Gynecologic, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, 300134, China.
Liang Zhang *Department of surgical oncology, Jiuquan Second Peoples Hospital, Jiuquan, 735000, China.
Wenpeng WangDepartment of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, China.
Lei ZhengDepartment of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, China.
Dalu KongDepartment of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, China.
Jiefu WangDepartment of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, China. wangjiefu@tjmuch.com.
Yang ZhanDepartment of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, China. zhanyang@tjmuch.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveColorectal cancer (CRC) is an aggressive malignancy with high mortality, and the identification of upstream regulators of stemness represents a critical step toward developing more effective targeted therapies. This study aimed to define the role of NR5A2 in CRC, particularly in the context of cancer stem cells (CSCs).

methodsWe profiled DNA copy number alterations, DNA methylation status, and mRNA expression in 30 CRC specimens. Primary CRC cells and CSC-enriched sphere cultures were established in vitro. Functional assays included RNA sequencing, sphere- and colony-formation assays, cell viability and cytotoxicity assessments, qRT-PCR, western blotting, immunofluorescence staining, chromatin immunoprecipitation (ChIP), and in vivo patient-derived xenograft (PDX) models.

resultsIntegrated genomic and epigenomic analyses implicated NR5A2 in the progression of an aggressive CRC subtype characterized by stemness gene expression. Our findings demonstrate that NR5A2 plays a key role in CRC. Mechanistically, NR5A2 promoted CSC maintenance by directly binding to the promoter and enhancer regions of NANOG, thereby upregulating its expression. Pharmacological inhibition of NR5A2 using Cmp3 significantly sensitized a subset of CRC PDX models to standard chemotherapy, resulting in enhanced tumor regression.

conclusionThis study identifies NR5A2 as a novel, actionable therapeutic target in CRC. Pharmacological modulation of NR5A2 disrupts CSC-driven stemness, potentially preventing relapse and improving treatment outcomes. These findings provide a strong rationale for the development of NR5A2-targeted therapies, either as monotherapy or in combination with chemotherapy, to optimize CRC patient care.

Indexed as

Colorectal NeoplasmsEpigenesis, GeneticNanog Homeobox ProteinNeoplastic Stem CellsAnimalsCell Line, TumorDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansMaleMiceReceptors, Cytoplasmic and NuclearNanog Homeobox ProteinNANOG protein, humanNR5A2 protein, humanReceptors, Cytoplasmic and NuclearCancer stem cellColorectal cancerEpigenetic regulationNANOGNR5A2

Identifiers

PMID41214698
PMCPMC12604224

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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.