Evidence map›Paper›PMID 23759586›Full record

ArticleCell cycle (Georgetown, Tex.)2013

Attenuation of dexamethasone-induced cell death in multiple myeloma is mediated by miR-125b expression.

Megan Y Murray, Stuart A Rushworth, Lyubov Zaitseva, Kristian M Bowles, David J Macewan

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

Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

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  17. Anti-Inflammatory Drugs as Anticancer Agents.International journal of molecular sciences · 2020
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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

5 authors at 3 institutions in 2 countries.

Megan Y MurrayNorwich Medical School, University of East Anglia, Norwich, UK.
Stuart A Rushworth
Lyubov Zaitseva
Kristian M Bowles
David J Macewan
Norwich University · USNorfolk and Norwich University Hospitals NHS Foundation Trust · GBUniversity of East Anglia · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dexamethasone is a key front-line chemotherapeutic for B-cell malignant multiple myeloma (MM). Dexamethasone modulates MM cell survival signaling but fails to induce marked cytotoxicity when used as a monotherapy. We demonstrate here the mechanism behind this insufficient responsiveness of MM cells toward dexamethasone, revealing in MM a dramatic anti-apoptotic role for microRNA (miRNA)-125b in the insensitivity toward dexamethasone-induced apoptosis. MM cells responding to dexamethasone exhibited enhanced expression of oncogenic miR-125b. Dexamethasone also induced expression of miR-34a, which acts to suppress SIRT1 deacetylase, and thus allows maintained acetylation and inactivation of p53. p53 mRNA is also suppressed by miR-125b targeting. Reporter assays showed that both these dexamethasone-induced miRNAs act downstream of their target genes to prevent p53 tumor suppressor actions and, ultimately, resist cytotoxic responses in MM. Use of antisense miR-125b transcripts enhanced expression of pro-apoptotic p53, repressed expression of anti-apoptotic SIRT1 and, importantly, significantly enhanced dexamethasone-induced cell death responses in MM. Pharmacological manipulations showed that the key regulation enabling complete dexamethasone sensitivity in MM cells lies with miR-125b. In summary, dexamethasone-induced miR-125b induces cell death resistance mechanisms in MM cells via the p53/miR-34a/SIRT1 signaling network and provides these cells with an enhanced level of resistance to cytotoxic chemotherapeutics. Clearly, such anti-apoptotic mechanisms will need to be overcome to more effectively treat nascent, refractory and relapsed MM patients. These mechanisms provide insight into the role of miRNA regulation of apoptosis and their promotion of MM cell proliferative mechanisms.

Indexed as

Antineoplastic Agents, HormonalApoptosisCell Line, TumorDexamethasoneDrug Resistance, NeoplasmHumansMicroRNAsMultiple MyelomaOligonucleotide Array Sequence AnalysisSignal TransductionSirtuin 1Transcriptional ActivationTranscriptomeTumor Suppressor Protein p53Antineoplastic Agents, HormonalDexamethasoneMicroRNAsMIRN125 microRNA, humanMIRN34 microRNA, humanSIRT1 protein, humanSirtuin 1TP53 protein, humanTumor Suppressor Protein p53mir-125bmir-34aNFκBp53SIRT1

Identifiers

PMID23759586
PMCPMC3737316
OpenAlexW1989259853

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.