Evidence map›Paper›PMID 38890707›Full record

ArticleClinical epigenetics2024

Estrogen-mediated DNMT1 and DNMT3A recruitment by EZH2 silences miR-570-3p that contributes to papillary thyroid malignancy through DPP4.

Xiarong Hu, Qingyao Ye, HuanQuan Lu, Zhiming Wu, Siyuan Chen, Ruinian Zheng

Abstract read
In one paragraph

Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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0cells of the map it votes in
4citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Xiarong Hu *Department of General Surgery, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China.
Qingyao Ye *Department of General Surgery, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China.
HuanQuan LuDepartment of General Surgery, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China.
Zhiming WuDepartment of General Surgery, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China.
Siyuan ChenDepartment of General Surgery, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China.
Ruinian ZhengDepartment of Oncology, Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China. zhengruinian.1983@163.com.

Funding

Dongguan Science and Technology of Social Development Program 20211800905222Guangdong Basic and Applied Basic Research Foundation 2021A1515010156, 2022A1515140134
6 · The paper itself

Abstract

backgroundPapillary thyroid carcinoma (PTC) is a common endocrine malignancy. Studies have indicated that estrogen can regulate the expression of miRNAs in numerous malignancies. MiR-570-3p has been shown to have a regulatory function in various cancers. However, studies of the regulatory function of miR-570-3p and a direct link between estrogen (especially estradiol E2) and miR-570-3p in PTC have not been done.

methodsExpression of miR-570-3p and its downstream target DPP4 in PTC tissues and cells was predicted using bioinformatics and validated by qRT-PCR and western blot assays. We then performed a series of gain-and-loss experiments to assess the functional significance of miR-570-3p/DPP4 axis in PTC progression in vitro and in vivo. Additionally, the methylation of the miR-570-3p promoter region was examined via bioinformatics analysis and MSP. Finally, the effects of E2 on PTC progression and the correlation between DNMT1/DNMT3A and EZH2 were predicted by bioinformatic tools and proved by luciferase reporter, ChIP, and co-IP assays.

resultsIn PTC tumor tissues and cell lines, there was a lower expression level and a higher methylation level of miR-570-3p compared to normal tissues and cell lines. DPP4 was identified as the downstream target of miR-570-3p. Overexpression of miR-570-3p reduced the proliferative, migratory, and invasive capabilities, and promoted apoptosis, while overexpression of DPP4 reversed these effects in PTC cells. It was also discovered that DNMT1 and DNMT3A increased the CpG methylation level of the miR-570-3p promoter in an EZH2-dependent manner, which led to decreased expression of miR-570-3p. Furthermore, we observed that estrogen (E2) enhanced the methylation of miR-570-3p and suppressed its expression levels, resulting in augmented tumor growth in vivo in PTC.

conclusionEstrogen regulates the EZH2/DNMTs/miR-570-3p/DPP4 signaling pathway to promote PTC progression.

Indexed as

Dipeptidyl Peptidase 4DNA (Cytosine-5-)-Methyltransferase 1DNA Methyltransferase 3AEnhancer of Zeste Homolog 2 ProteinEstrogensGene Expression Regulation, NeoplasticMicroRNAsThyroid Cancer, PapillaryThyroid NeoplasmsAnimalsCell Line, TumorCell ProliferationDNA (Cytosine-5-)-MethyltransferasesDNA MethylationFemaleHumansDipeptidyl Peptidase 4DNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT1 protein, humanDNMT3A protein, humanDPP4 protein, humanEnhancer of Zeste Homolog 2 ProteinEstrogensEZH2 protein, humanMicroRNAsDPP4EstrogenMethylationmiR-570-3pPapillary thyroid carcinoma

Identifiers

PMID38890707
PMCPMC11184720

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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.