Evidence map›Paper›PMID 41217933›Full record

ArticleCell reports2025

Feedforward miR-181d degradation modulates population variance of methyl-guanine methyl transferase and temozolomide resistance.

Gatikrushna Singh, Shilpi Singh, Iteeshree Mohapatra, Stefan Kim, Mayur Sharma, Johnny Akers, Thien Nguyen, Eric Wong, Margot Martinez Moreno, Efrosini Kokkoli and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

15 authors.

Gatikrushna SinghDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: gsingh@umn.edu.
Shilpi SinghDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Iteeshree MohapatraDepartment of Veterinary Biomedical Sciences, St. Paul, MN 55108, USA.
Stefan KimDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Mayur SharmaDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Johnny AkersVisiCELL Medical Inc., San Diego, CA 92121, USA.
Thien NguyenDepartment of Pediatrics, Stanford University, Stanford, CA 94304, USA.
Eric WongDepartment of Neurology, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI 02903, USA.
Margot Martinez MorenoDepartment of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI 02903, USA.
Efrosini KokkoliDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Shobha VasudevanDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02903, USA.
Sean E LawlerDepartment of Pathology and Laboratory Medicine, Legorreta Cancer Center, Brown University, Providence, RI 02903, USA.
Wafik S El-DeiryDepartment of Pathology and Laboratory Medicine, Legorreta Cancer Center, Brown University, Providence, RI 02903, USA.
Ziya GokaslanDepartment of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI 02903, USA.
Clark C ChenDepartment of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI 02903, USA.

Funding

Targeting Mechanisms of Acquired Temozolomide Resistance in GlioblastomaR01NS097649 · NINDS · UNIVERSITY OF MINNESOTA · PI CHEN, CLARK CHIN-CHUNG · 2016 to 2021
$1.7M
NINDS NIH HHS R01 NS097649
6 · The paper itself

Abstract

Intratumoral heterogeneity plays a pivotal role in cancer evolution, providing the substrate for adaptation to selective pressures, including chemotherapy treatment. Here, we demonstrate that miR-181d modulates variability in methyl-guanine methyl transferase (MGMT) expression, contributing to this heterogeneity in glioblastoma, the most common form of adult primary brain tumor. Treatment with standard-of-care temozolomide (TMZ) chemotherapy triggers a feedforward loop that accelerates polyribonucleotide nucleotidyltransferase 1 (PNPT1)-dependent miR-181d degradation. This degradation requires the activation of ataxia-telangiectasia and Rad3-related (ATR) kinase. The degradation of miR-181d in glioblastoma cells increases the variance of MGMT expression in the cell population, contributing to acquired TMZ resistance. This resistance is suppressed by exogenously transfected miR-181d. These findings suggest that microRNA regulates intratumoral heterogeneity by modulating the transcriptional variability of key DNA repair enzymes, providing a compelling rationale for miRNA delivery as a platform for glioblastoma therapy.

Indexed as

Brain NeoplasmsDacarbazineDNA Modification MethylasesDNA Repair EnzymesDrug Resistance, NeoplasmGlioblastomaMicroRNAsTumor Suppressor ProteinsAntineoplastic Agents, AlkylatingAtaxia Telangiectasia Mutated ProteinsCell Line, TumorExoribonucleasesGene Expression Regulation, NeoplasticHumansTemozolomideAntineoplastic Agents, AlkylatingAtaxia Telangiectasia Mutated ProteinsATR protein, humanDacarbazineDNA Modification MethylasesDNA Repair EnzymesExoribonucleasesMGMT protein, humanMicroRNAsMIrn181 microRNA, humanTemozolomideTumor Suppressor ProteinsATRCP: cancerglioblastomaMGMTmicroRNAPNPT1temozolomide

Identifiers

PMID41217933
PMCPMC12767607

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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.