Evidence map›Paper›PMID 26913599›Full record

ArticleCell death & disease2016

The miR-27a-calreticulin axis affects drug-induced immunogenic cell death in human colorectal cancer cells.

T Colangelo, G Polcaro, P Ziccardi, L Muccillo, M Galgani, B Pucci, M Rita Milone, A Budillon, M Santopaolo, G Mazzoccoli and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 9% 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

54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. miRNA-Based Technologies in Cancer Therapy.Journal of personalized medicine · 2023
    Review
  14. Review
  15. Calreticulin as a marker and therapeutic target for cancer.Clinical and experimental medicine · 2023
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Huaier Induces Immunogenic Cell DeathFrontiers in cell and developmental biology · 2022
    Article
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

13 authors at 5 institutions in 1 country.

T ColangeloDepartment of Sciences and Technologies, University of Sannio, Benevento 82100, Italy.
G PolcaroDepartment of Sciences and Technologies, University of Sannio, Benevento 82100, Italy.
P ZiccardiDepartment of Sciences and Technologies, University of Sannio, Benevento 82100, Italy.
L MuccilloDepartment of Sciences and Technologies, University of Sannio, Benevento 82100, Italy.
M GalganiIstituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Napoli 80131, Italy.ORCID http://orcid.org/0000-0001-8414-1676
B PucciCentro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Mercogliano (AV) 83013, Italy.
M Rita MiloneCentro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Mercogliano (AV) 83013, Italy.
A BudillonCentro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Mercogliano (AV) 83013, Italy.
M SantopaoloDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II", Napoli 80131, Italy.
G MazzoccoliDivision of Internal Medicine and Chronobiology Unit, IRCCS - "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG) 71013, Italy.ORCID http://orcid.org/0000-0003-3535-7635
G MatareseIstituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Napoli 80131, Italy.
L SabatinoDepartment of Sciences and Technologies, University of Sannio, Benevento 82100, Italy.
V ColantuoniDepartment of Sciences and Technologies, University of Sannio, Benevento 82100, Italy.
University of Sannio · ITIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale" · ITInstitute for Experimental Endocrinology and Oncology · ITCasa Sollievo della Sofferenza · ITUniversity of Naples Federico II · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunogenic cell death (ICD) evoked by chemotherapeutic agents implies emission of selected damage-associated molecular patterns (DAMP) such as cell surface exposure of calreticulin, secretion of ATP and HMGB1. We sought to verify whether miR-27a is implicated in ICD, having demonstrated that it directly targets calreticulin. To this goal, we exposed colorectal cancer cell lines, genetically modified to express high or low miR-27a levels, to two bona fide ICD inducers (mitoxantrone and oxaliplatin). Low miR-27a-expressing cells displayed more ecto-calreticulin on the cell surface and increased ATP and HMGB1 secretion than high miR-27a-expressing ones in time-course experiments upon drug exposure. A calreticulin target protector counteracted the miR-27a effects while specific siRNAs mimicked them, confirming the results reported. In addition, miR-27a negatively influenced the PERK-mediated route and the late PI3K-dependent secretory step of the unfolded protein response to endoplasmic reticulum stress, suggesting that miR-27a modulates the entire ICD program. Interestingly, upon chemotherapeutic exposure, low miR-27a levels associated with an earlier and stronger induction of apoptosis and with morphological and molecular features of autophagy. Remarkably, in ex vivo setting, under the same chemotherapeutic induction, the conditioned media from high miR-27a-expressing cells impeded dendritic cell maturation while increased the secretion of specific cytokines (interleukin (IL)-4, IL-6, IL-8) and negatively influenced CD4(+) T-cell interferon γ production and proliferation, all markers of a tumor immunoevasion strategy. In conclusion, we provide the first evidence that miR-27a impairs the cell response to drug-induced ICD through the regulatory axis with calreticulin.

Indexed as

ApoptosisAntineoplastic AgentsCalreticulinCD4-Positive T-LymphocytesCell Line, TumorCell ProliferationColorectal NeoplasmsDendritic CellsDown-RegulationEndoplasmic Reticulum StressHCT116 CellsHumansInterferon-gammaInterleukinsMicroRNAsMitoxantroneAntineoplastic AgentsCalreticulinInterferon-gammaInterleukinsMicroRNAsMitoxantroneOligonucleotides, AntisenseOrganoplatinum CompoundsOxaliplatinPhosphatidylinositol 3-Kinases

Identifiers

PMID26913599
PMCPMC4849155
OpenAlexW2283970331

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.