Evidence map›Paper›PMID 33066331›Full record

ArticleInternational journal of molecular sciences2020

Hypoxic Melanoma Cells Deliver microRNAs to Dendritic Cells and Cytotoxic T Lymphocytes through Connexin-43 Channels.

Andrés Tittarelli, Mariela Navarrete, Marcelo Lizana, Francisca Hofmann-Vega, Flavio Salazar-Onfray

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy.International journal of molecular sciences · 2022
    Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Perspective and Therapeutic Potential of the Noncoding RNA-Connexin Axis.International journal of molecular sciences · 2024
    Review
  9. Predicting miRNA-Disease Associations by Combining Graph and Hypergraph Convolutional Network.Interdisciplinary sciences, computational life sciences · 2024
    Article
  10. Article
  11. Review
  12. A New Approach to Melanoma Treatment: microRNAs.Current topics in medicinal chemistry · 2024
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. 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

5 authors at 3 institutions in 1 country.

Andrés TittarelliPrograma Institucional de Fomento a la Investigación, Desarrollo e Innovación (PIDi), Universidad Tecnológica Metropolitana (UTEM), 8940577 Santiago, Chile.
Mariela NavarreteDisciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile.
Marcelo LizanaDisciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile.
Francisca Hofmann-VegaDisciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile.
Flavio Salazar-OnfrayDisciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile.ORCID 0000-0002-1848-5697
Millennium Institute on Immunology and Immunotherapy · CLUniversity of Chile · CLMetropolitan University of Technology · CL

Funding

Fondo Nacional de Desarrollo Científico y Tecnológico Fondecyt 11160380Fondo Nacional de Desarrollo Científico y Tecnológico Fondecyt 1171213Millennium Science Initiative from the Ministry for the Economy, Development and Tourism P09/016-F
6 · The paper itself

Abstract

Alterations in microRNA (miRNA) profiles, induced by tumor microenvironment stressors, like hypoxia, allow cancer cells to acquire immune-resistance phenotypes. Indeed, hypoxia-induced miRNAs have been implicated in cancer progression through numerous cancer cell non-autonomous mechanisms, including the direct transfer of hypoxia-responsive miRNA from cancer to immune cells via extracellular vesicles. Connexin-43 (Cx43)-constituted gap junctions (GJs) have also been involved in miRNA intercellular mobilization, in other biological processes. In this report, we aimed to evaluate the involvement of Cx43-GJs in the shift of miRNAs induced by hypoxia, from hypoxic melanoma cells to dendritic cells and melanoma-specific cytotoxic T lymphocytes (CTLs). Using qRT-PCR arrays, we identified that miR-192-5p was strongly induced in hypoxic melanoma cells. Immune cells acquired this miRNA after co-culture with hypoxic melanoma cells. The transfer of miR-192-5p was inhibited when hypoxic melanoma cells expressed a dominant negative Cx43 mutant or when Cx43 expression was silenced using specific short-hairpin RNAs. Interestingly, miR-192-5p levels on CTLs after co-culture with hypoxic melanoma cells were inversely correlated with the cytotoxic activity of T cells and with ZEB2 mRNA expression, a validated immune-related target of miR-192-5p, which is also observed in vivo. Altogether, our data suggest that hypoxic melanoma cells may suppress CTLs cytotoxic activity by transferring hypoxia-induced miR-192-5p through a Cx43-GJs driven mechanism, constituting a resistance strategy for immunological tumor escape.

Indexed as

Tumor HypoxiaAnimalsCell Line, TumorConnexin 43Dendritic CellsGap JunctionsHumansMelanomaMiceMice, Inbred C57BLMicroRNAsT-Lymphocytes, CytotoxicConnexin 43MicroRNAsMirn192 microRNA, mouseconnexin-43cytotoxic T lymphocytesdendritic cellshypoxiamap junctionsmelanomamicroRNAsmiR-192zeb2

Identifiers

PMID33066331
PMCPMC7589225
OpenAlexW3093085774

What Socratic holds

Textmetadata
LicenceCC BY
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.