Evidence map›Paper›PMID 33229509›Full record

ArticleJournal for immunotherapy of cancer2020

Wrinkle in the plan: miR-34a-5p impacts chemokine signaling by modulating CXCL10/CXCL11/CXCR3-axis in CD4

Martin Hart, Laura Nickl, Barbara Walch-Rueckheim, Lena Krammes, Stefanie Rheinheimer, Caroline Diener, Tanja Taenzer, Tim Kehl, Martina Sester, Hans-Peter Lenhof and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

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  19. Trials and Tribulations of MicroRNA Therapeutics.International journal of molecular sciences · 2024
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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

12 authors at 1 institution in 2 countries.

Martin Hart *Institute of Human Genetics, Saarland University, 66421 Homburg, Germany martin.hart@uks.eu.ORCID 0000-0001-9361-8106
Laura Nickl *Institute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Barbara Walch-RueckheimInstitute of Virology and Center of Human & Molecular Biology, Saarland University, 66421 Homburg, Germany.
Lena KrammesInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Stefanie RheinheimerInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Caroline DienerInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Tanja TaenzerInstitute of Virology and Center of Human & Molecular Biology, Saarland University, 66421 Homburg, Germany.
Tim KehlCenter for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Martina SesterDepartment of Transplant and Infection Immunology, Saarland University, 66421 Homburg, Germany.
Hans-Peter LenhofCenter for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Andreas KellerChair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Eckart MeeseInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Saarland University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn 2016 the first-in-human phase I study of a miRNA-based cancer therapy with a liposomal mimic of microRNA-34a-5p (miR-34a-5p) was closed due to five immune related serious adverse events (SAEs) resulting in four patient deaths. For future applications of miRNA mimics in cancer therapy it is mandatory to unravel the miRNA effects both on the tumor tissue and on immune cells. Here, we set out to analyze the impact of miR-34a-5p over-expression on the CXCL10/CXCL11/CXCR3 axis, which is central for the development of an effective cancer control.

methodsWe performed a whole genome expression analysis of miR-34a-5p transfected M1 macrophages followed by an over-representation and a protein-protein network analysis. In-silico miRNA target prediction and dual luciferase assays were used for target identification and verification. Target genes involved in chemokine signaling were functionally analyzed in M1 macrophages, CD4

resultsA whole genome expression analysis of M1 macrophages with induced miR-34a-5p over-expression revealed an interaction network of downregulated target mRNAs including

conclusionsMiR-34a-5p mimic administered by intravenous administration will likely not only be up-taken by the tumor cells but also by the immune cells. Our results indicate that miR-34a-5p over-expression leads in M1 macrophages to a reduced secretion of CXCL10 and CXCL11 chemokines and in CD4

Indexed as

CD4-Positive T-LymphocytesCD8-Positive T-LymphocytesChemokine CXCL10Chemokine CXCL11HEK293 CellsHumansMacrophagesMicroRNAsReceptors, CXCR3RNA, MessengerSignal TransductionChemokine CXCL10Chemokine CXCL11CXCL10 protein, humanCXCL11 protein, humanCXCR3 protein, humanMicroRNAsMIRN34 microRNA, humanReceptors, CXCR3RNA, MessengerCD4-Positive T-Lymphocytescytokinesgene expression profilingimmunotherapymacrophages

Identifiers

PMID33229509
PMCPMC7684812
OpenAlexW3110059254

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.