Evidence map›Paper›PMID 27773931›Full record

ArticleLeukemia2017

The LIN28B/let-7 axis is a novel therapeutic pathway in multiple myeloma.

S Manier, J T Powers, A Sacco, S V Glavey, D Huynh, M R Reagan, K Z Salem, M Moschetta, J Shi, Y Mishima and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing 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

56 citing papers in PubMed.

  1. Review
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  7. The FGF/FGFR/c-Myc axis as a promising therapeutic target in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2024
    Review
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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

15 authors.

S ManierDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
J T PowersDivision of Pediatric Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston MA, USA.
A SaccoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
S V GlaveyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
D HuynhDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M R ReaganDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
K Z SalemDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M MoschettaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
J ShiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Y MishimaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
C Roche-LestienneJean-Pierre Aubert Research Centre, INSERM U1172, University Lille 2, Lille, France.
X LeleuService des Maladies du Sang, CHRU Lille, Lille, France.
A M RoccaroDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
G Q DaleyDivision of Pediatric Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston MA, USA.
I M GhobrialDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Funding

The role of miRNA15a and 16-1 in Multiple MyelomaR01CA154648 · NCI · DANA-FARBER CANCER INST · PI GHOBRIAL, IRENE M. · 2011 to 2015
$1.8M
Targeting cell trafficking as a new therapeutic modality for Multiple MyelomaR01CA133799 · NCI · DANA-FARBER CANCER INST · PI GHOBRIAL, IRENE M. · 2008 to 2011
$1.4M
NCI NIH HHS R01 CA133799NCI NIH HHS R01 CA154648
6 · The paper itself

Abstract

MYC is a major oncogenic driver of multiple myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA-sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM. We provide proof of principle for therapeutic regulation of MYC through let-7 with an LNA-GapmeR (locked nucleic acid-GapmeR) containing a let-7b mimic in vivo, demonstrating that high levels of let-7 expression repress tumor growth by regulating MYC expression. These findings reveal a novel mechanism of therapeutic targeting of MYC through the LIN28B/let-7 axis in MM that may impact other MYC-dependent cancers as well.

Indexed as

Gene Expression Regulation, NeoplasticRNA InterferenceAnimalsCase-Control StudiesCell CycleCell Line, TumorCluster AnalysisDisease Models, AnimalGene Expression ProfilingGenes, mycHeterograftsHumansMiceMicroRNAsMultiple MyelomaPrognosisLIN28B protein, humanMicroRNAsmirnlet7 microRNA, humanRNA-Binding Proteins

Identifiers

PMID27773931
PMCPMC5382134

What OpenQuestion holds

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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.