Evidence map›Paper›PMID 39614338›Full record

ArticleBreast cancer research : BCR2024

Gremlin-2 is a novel tumor suppressor that negatively regulates ID1 in breast cancer.

Jiwoo Jung, Na Hui Kim, Jayeon Park, Dayeon Lim, Minji Kwon, World Gil, Suyeon Jung, Minjeong Go, Chaeeon Kim, Ye Hwang Cheong and 4 more

Abstract read
In one paragraph

Article in Breast cancer research : BCR, 2024. 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. Endometriosis: An Immunologist's Perspective.International journal of molecular sciences · 2025
    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

14 authors.

Jiwoo Jung *Department of Medical Sciences, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Na Hui Kim *Department of ICT Environmental Health System, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Jayeon ParkDepartment of Medical Sciences, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Dayeon LimDepartment of Medical Sciences, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Minji KwonDepartment of Medical Sciences, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
World GilDepartment of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Suyeon JungDepartment of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Minjeong GoDepartment of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Chaeeon KimDepartment of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Ye Hwang CheongDrug Discovery Research Laboratories, Dong-A ST Co., Ltd, Yongin, 17073, Republic of Korea.
Mee-Hyun LeeCollege of Korean Medicine, Dongshin University, Naju, 58245, Republic of Korea.
Hee Sun ParkDivision of Pulmonology, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.
Yong-Bin EomDepartment of Medical Sciences, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Sin-Aye ParkDepartment of Medical Sciences, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea. sappark@sch.ac.kr.

Funding

National Research Foundation of Korea 2022R1F1A1074226
6 · The paper itself

Abstract

backgroundBreast cancer is one of the most common cancers in women and is closely associated with obesity. Gremlin-2 (GREM2), an antagonist for bone morphogenetic proteins (BMPs), has been considered an inhibitor of adipogenic differentiation in adipose-derived stromal/stem cells. However, the role of GREM2 in breast cancer cells remains largely unknown, and its signaling mechanism has yet to be clarified.

methodsBioinformatics analysis was conducted using public databases. Breast cancer cells overexpressing mock or GREM2 were used for in vitro and in vivo studies. Cell viability, colony formation, migration, and animal studies were performed to investigate the role of GREM2 in breast cancer cells. Screening of target genes affected by GREM2 overexpression in breast cancer cells was performed through RNA sequencing (RNA-seq) analysis.

resultsThe expression level of GREM2 mRNA was significantly reduced in both breast cancer tissues and cell lines. Kaplan-Meier analysis showed that low expression of GREM2 and high methylation of the GREM2 promoter were each associated with poor patient survival. The low mRNA expression of GREM2 in breast cancer cells was increased by the demethylating agent decitabine. Breast cancer cells overexpressing GREM2 decreased cell proliferation when compared to control cells, both in vitro and in vivo. Through comparison of RNA-seq analysis between cell lines and tissue samples, gene ontologies that were consistently upregulated or downregulated by GREM2 in breast cancer were identified. In particular, the expression of inhibitor of DNA-binding-1 (ID1) was repressed by GREM2. BMP2 is one of the upstream regulators that increases the expression of ID1, and the expression of ID1 reduced by GREM2 was restored by overexpression of BMP2. Also, the migration ability of breast cancer cells, which had been suppressed by GREM2, was restored by BMP2 or ID1.

conclusionsLow expression of GREM2 in breast cancer cells is associated with hypermethylation of the GREM2 promoter, which may ultimately contribute to poor patient survival. GREM2 participates in regulating the expression of various genes, including ID1, and is involved in suppressing the proliferation of breast cancer cells. This suggests that GREM2 has the potential to act as a novel tumor suppressor in breast cancer.

Indexed as

Breast NeoplasmsCell ProliferationDNA MethylationGene Expression Regulation, NeoplasticInhibitor of Differentiation Protein 1AnimalsCell Line, TumorCell MovementCytokinesFemaleGenes, Tumor SuppressorHumansIntercellular Signaling Peptides and ProteinsMicePrognosisPromoter Regions, GeneticCytokinesGREM2 protein, humanID1 protein, humanInhibitor of Differentiation Protein 1Intercellular Signaling Peptides and ProteinsBreast cancerGremlin-2HypermethylationInhibitor of DNA-binding-1RNA sequencingTumor suppressor

Identifiers

PMID39614338
PMCPMC11606173

What Socratic 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 Socratic graph.