Evidence map›Paper›PMID 29988076›Full record

ArticleCell death and differentiation2019

SREBP1, targeted by miR-18a-5p, modulates epithelial-mesenchymal transition in breast cancer via forming a co-repressor complex with Snail and HDAC1/2.

Ning Zhang, Hanwen Zhang, Ying Liu, Peng Su, Jiashu Zhang, Xiaolong Wang, Mingjuan Sun, Bing Chen, Wenjing Zhao, Lijuan Wang and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 1 pooled it
8.7field-weighted citation impact, top 1% of its field
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

107 citing papers in PubMed, 1 synthesis or guideline pooled it, 233 citations in OpenAlex.

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47 more citing papers are in PubMed but not listed here.

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 at 5 institutions in 2 countries.

Ning ZhangDepartment of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Hanwen ZhangDepartment of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Ying LiuDepartment of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Peng SuDepartment of Pathology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Jiashu ZhangDepartment of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Xiaolong WangDepartment of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Mingjuan SunShandong Cancer Hospital affiliated to Shandong University, Ji'nan, Shandong, China.
Bing ChenPathology Tissue Bank, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Wenjing ZhaoPathology Tissue Bank, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Lijuan WangPathology Tissue Bank, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Huiyun WangState Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
Meena S MoranDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.
Bruce G HafftyDepartment of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Qifeng YangDepartment of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, Shandong, China. qifengy_sdu@163.com.ORCID http://orcid.org/0000-0003-0576-8513
Qilu Hospital of Shandong University · CNRutgers, The State University of New Jersey · USShandong University · CNSun Yat-sen University · CNYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

The progression of localized breast cancer to distant metastasis results in a poor prognosis and a high mortality rate. In this study, the contributions of miRNAs to tumor progression and the regulatory mechanisms leading to their expression alterations were investigated. Using highly lung-metastatic sub-lines from parental breast cancer cells, miRNA expression profiling revealed that the miR-17-92 cluster is significantly downregulated and the miR-18a-5p is the most evidently decreased. Ectopic expression and inhibition of miR-18a-5p demonstrated its capacity in suppressing migration and invasion of breast cancer cells. Further research identified sterol regulatory element binding transcription protein 1 (SREBP1), the master transcription factor that controls lipid metabolism, as a candidate target of miR-18a-5p. SREBP1 is overexpressed and strongly associated with worse clinical outcomes in breast cancer. Functionally SREBP1 promotes growth and metastasis of breast cancer both in vitro and in vivo. To unravel the underlying mechanism of SREBP1-mediated metastasis, mRNA profiling and subsequent gene set enrichment analyses (GSEA) were performed and SREBP1 was demonstrated to be significantly associated with epithelial-mesenchymal transition (EMT). Furthermore, SREBP1-mediated repression of E-cadherin was found to be deacetylation dependent and was augmented by recruiting Snail/HDAC1/2 repressor complex. In the light of these data, we propose that reduced expression of miR-18a-5p and concomitant overexpression of SREBP1 lead to induction of EMT states that in turn, promote breast cancer progression and metastasis. Taken together, our study reveals the crucial role of miR-18a-5p and SREBP1 in the EMT and metastasis, thus providing promising drug targets for tailored therapy in the advanced breast cancer setting.

Indexed as

AnimalsBreast NeoplasmsCadherinsCell MovementCell ProliferationEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHeterograftsHistone Deacetylase 1Histone Deacetylase 2HumansMCF-7 CellsMiceMicroRNAsMiddle AgedCadherinsHDAC1 protein, humanHDAC2 protein, humanHistone Deacetylase 1Histone Deacetylase 2MicroRNAsMIRN18A microRNA, humanSNAI1 protein, humanSnail Family Transcription FactorsSREBF1 protein, humanSterol Regulatory Element Binding Protein 1

Identifiers

PMID29988076
PMCPMC6461794
OpenAlexW2815290681

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.