Evidence map›Paper›PMID 23045278›Full record

ArticleOncogene2013

miR-141 regulates KEAP1 and modulates cisplatin sensitivity in ovarian cancer cells.

M T M van Jaarsveld, J Helleman, A W M Boersma, P F van Kuijk, W F van Ijcken, E Despierre, I Vergote, R H J Mathijssen, E M J J Berns, J Verweij and 2 more

Abstract read
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In one paragraph

Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% 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

124 citing papers in PubMed, 1 synthesis or guideline pooled it, 219 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. The TGFβ2-Snail1-miRNAClinical and translational medicine · 2024
    Article
  7. Role of Epigenetics for the Efficacy of Cisplatin.International journal of molecular sciences · 2024
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64 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

12 authors at 3 institutions in 2 countries.

M T M van JaarsveldDepartment of Medical Oncology, Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
J Helleman
A W M Boersma
P F van Kuijk
W F van Ijcken
E Despierre
I Vergote
R H J Mathijssen
E M J J Berns
J Verweij
J Pothof
E A C Wiemer
Erasmus MC · NLErasmus University Rotterdam · NLEuropean Union · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epithelial ovarian cancer is the most lethal gynecological malignancy in the Western world. A major impediment for the successful treatment is the development of drug resistance. The molecular processes that contribute to resistance have been extensively studied; however, there is not much known about regulation by microRNAs (miRNAs). We compared miRNA expression profiles of an isogenic cisplatin-sensitive and -resistant ovarian cancer cell line pair (A2780/A2780 DDP) and found 27 miRNAs to be differentially expressed (2-fold). Five of these, including the family members miR-141/200c, showed a correlation with cisplatin sensitivity in the NCI-60 panel. Overexpression of miR-141 resulted in enhanced resistance to cisplatin in ovarian cancer cell lines. We next correlated the expression level of miR-141 in 132 primary ovarian tumors (108 serous and 24 non-serous) with response to platinum-based chemotherapy. Although no differences were observed in the serous tumors, miR-141 levels were higher in non-serous ovarian tumors that did not respond well to therapy (platinum-free interval <6 months). We demonstrate that miR-141 directly targets KEAP1, and that downregulation of KEAP1 induces cisplatin resistance. Conversely, overexpression of KEAP1 significantly enhanced cisplatin sensitivity. Expression of KEAP1 with its 3'-UTR, and a 3'-UTR in which the miR-141 target site has been mutated, revealed that miR-141 regulates KEAP1 upon exposure to cisplatin. Finally, we show that the NF-κB pathway, which can be regulated by KEAP1, is activated upon miR-141 overexpression, and that inhibition of this pathway partially reverses miR-141-mediated cisplatin resistance. These findings demonstrate that the miR-141-mediated regulation of KEAP1 has a crucial role in the cellular response to cisplatin.

Indexed as

Gene Expression Regulation, NeoplasticAdultAgedAged, 80 and overAntineoplastic AgentsCell Line, TumorCisplatinCluster AnalysisDrug Resistance, NeoplasmFemaleGene ExpressionGene Expression ProfilingHumansIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1MicroRNAsAntineoplastic AgentsCisplatinIntracellular Signaling Peptides and ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1MicroRNAsMIRN141 microRNA, humanMIRN200 microRNA, humanNF-kappa B

Identifiers

PMID23045278
OpenAlexW2003624918

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.