Evidence map›Paper›PMID 31733056›Full record

ArticleNucleic acids research2019

A DNA aptamer for binding and inhibition of DNA methyltransferase 1.

Linlin Wang, Ju Yong Lee, Linfeng Gao, Jiekai Yin, Yaokai Duan, Luis A Jimenez, Gary Brent Adkins, Wendan Ren, Linhui Li, Jian Fang and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

22 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
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  8. A biomechanical view of epigenetic tumor regulation.Journal of biological physics · 2023
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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

13 authors at 1 institution in 1 country.

Linlin WangDepartment of Chemistry, University of California-Riverside, Riverside, CA 92521, USA.
Ju Yong LeeDepartment of Chemistry, University of California-Riverside, Riverside, CA 92521, USA.
Linfeng GaoEnvironmental Toxicology Graduate Program, University of California-Riverside, Riverside, CA 92521, USA.
Jiekai YinEnvironmental Toxicology Graduate Program, University of California-Riverside, Riverside, CA 92521, USA.
Yaokai DuanDepartment of Chemistry, University of California-Riverside, Riverside, CA 92521, USA.
Luis A JimenezProgram in Biomedical Sciences, University of California-Riverside, Riverside, CA 92521, USA.
Gary Brent AdkinsDepartment of Chemistry, University of California-Riverside, Riverside, CA 92521, USA.
Wendan RenDepartment of Biochemistry, University of California-Riverside, Riverside, CA 92521, USA.
Linhui LiDepartment of Biochemistry, University of California-Riverside, Riverside, CA 92521, USA.
Jian FangDepartment of Biochemistry, University of California-Riverside, Riverside, CA 92521, USA.
Yinsheng WangDepartment of Chemistry, University of California-Riverside, Riverside, CA 92521, USA.
Jikui SongEnvironmental Toxicology Graduate Program, University of California-Riverside, Riverside, CA 92521, USA.
Wenwan ZhongDepartment of Chemistry, University of California-Riverside, Riverside, CA 92521, USA.
University of California, Riverside · US

Funding

Research Training in Environmental ToxicologyT32ES018827 · NIEHS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Yinsheng Wang · 2010 to 2026
$5.3M
Mechanistic Insights into Mammalian DNA MethylationR35GM119721 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Jikui Song · 2016 to 2026
$5.3M
Quantitative Adductomics Approaches for Assessing the Occurrence and Repair of DNA AdductsR01CA210072 · NCI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI WANG, YINSHENG · 2017 to 2021
$1.8M
3-Dimensional profile of circulating miRNA for early cancer detectionR01CA188991 · NCI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI ZHONG, WENWAN · 2015 to 2018
$1.3M
NCI NIH HHS R01 CA188991NCI NIH HHS R01 CA210072NIEHS NIH HHS T32 ES018827NIGMS NIH HHS R35 GM119721
6 · The paper itself

Abstract

DNA methyltransferases (DNMTs) are enzymes responsible for establishing and maintaining DNA methylation in cells. DNMT inhibition is actively pursued in cancer treatment, dominantly through the formation of irreversible covalent complexes between small molecular compounds and DNMTs that suffers from low efficacy and high cytotoxicity, as well as no selectivity towards different DNMTs. Herein, we discover aptamers against the maintenance DNA methyltransferase, DNMT1, by coupling Asymmetrical Flow Field-Flow Fractionation (AF4) with Systematic Evolution of Ligands by EXponential enrichment (SELEX). One of the identified aptamers, Apt. #9, contains a stem-loop structure, and can displace the hemi-methylated DNA duplex, the native substrate of DNMT1, off the protein on sub-micromolar scale, leading for effective enzymatic inhibition. Apt. #9 shows no inhibition nor binding activity towards two de novo DNMTs, DNMT3A and DNMT3B. Intriguingly, it can enter cancer cells with over-expression of DNMT1, colocalize with DNMT1 inside the nuclei, and inhibit the activity of DNMT1 in cells. This study opens the possibility of exploring the aptameric DNMT inhibitors being a new cancer therapeutic approach, by modulating DNMT activity selectively through reversible interaction. The aptamers could also be valuable tools for study of the functions of DNMTs and the related epigenetic mechanisms.

Indexed as

Aptamers, NucleotideCell Line, TumorCell ProliferationDeoxycytidineDNA (Cytosine-5-)-Methyltransferase 1DNA MethylationEpigenesis, GeneticHEK293 CellsHeLa CellsHumansNeoplasms5-methyldeoxycytidineAptamers, NucleotideDeoxycytidineDNA (Cytosine-5-)-Methyltransferase 1DNMT1 protein, human

Identifiers

PMID31733056
PMCPMC7145629
OpenAlexW2987527092

What OpenQuestion holds

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LicenceCC BY-NC
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.