Evidence map›Paper›PMID 17686970›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2007

A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance.

Prasun J Mishra, Rita Humeniuk, Pravin J Mishra, Giuseppe S A Longo-Sorbello, Debabrata Banerjee, Joseph R Bertino

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
188citing papers in PubMed, 2 pooled it
16.2field-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

188 citing papers in PubMed, 2 syntheses or guidelines pooled it, 417 citations in OpenAlex.

  1. Pooled it
  2. Pri-miR-34b/c rs4938723 TC heterozygote is associated with increased cancer risks: evidence from published data.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
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  17. Association ofBioscience reports · 2019
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128 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

6 authors at 2 institutions in 1 country.

Prasun J MishraDepartment of Pharmacology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA.
Rita Humeniuk
Pravin J Mishra
Giuseppe S A Longo-Sorbello
Debabrata Banerjee
Joseph R Bertino
Rutgers, The State University of New Jersey · USRutgers Cancer Institute of New Jersey

Funding

NCI NIH HHS CA0810
6 · The paper itself

Abstract

MicroRNAs are predicted to regulate approximately 30% of all human genes by targeting sequences in their 3' UTR. Polymorphisms in 3' UTR of several genes have been reported to affect gene expression, but the mechanism is not fully understood. Here, we demonstrate that 829C-->T, a naturally occurring SNP, near the miR-24 binding site in the 3' UTR of human dihydrofolate reductase (DHFR) affects DHFR expression by interfering with miR-24 function, resulting in DHFR overexpression and methotrexate resistance. miR-24 has a conserved binding site in DHFR 3' UTR. DHFR with WT and 3' UTR containing the 829C-->T mutation were expressed in DG44 cells that lack DHFR. Overexpression of miR-24 in cells with WT DHFR resulted in down-regulation of DHFR protein, whereas no effect on DHFR protein expression was observed in the mutant 3' UTR-expressing cells. Inhibition of endogenous miR-24 with a specific inhibitor led to up-regulation of DHFR in WT and not in mutant cells. Cells with the mutant 3' UTR had a 2-fold increase in DHFR mRNA half-life, expressed higher DHFR mRNA and DHFR protein, and were 4-fold more resistant to methotrexate as compared with WT cells. SNP-829C-->T, therefore, leads to a decrease in microRNA binding leading to overexpression of its target and results in resistance to methotrexate. We demonstrate that a naturally occurring miRSNP (a SNP located at or near a microRNA binding site in 3' UTR of the target gene or in a microRNA) is associated with enzyme overproduction and drug resistance.

Indexed as

Polymorphism, Single NucleotideAnimalsBase SequenceBinding SitesCHO CellsCricetinaeCricetulusMicroRNAsMolecular Sequence DataMutagenesis, Site-DirectedRNA, MessengerTetrahydrofolate DehydrogenaseMicroRNAsRNA, MessengerTetrahydrofolate Dehydrogenase

Identifiers

PMID17686970
PMCPMC1948927
OpenAlexW1985825541

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.