Evidence map›Paper›PMID 35406401›Full record

ArticleCancers2022

5-Azacytidine Downregulates the Proliferation and Migration of Hepatocellular Carcinoma Cells In Vitro and In Vivo by Targeting miR-139-5p/ROCK2 Pathway.

Federica Tonon, Maja Cemazar, Urska Kamensek, Cristina Zennaro, Gabriele Pozzato, Sergio Caserta, Flora Ascione, Mario Grassi, Stefano Guido, Cinzia Ferrari and 15 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
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  5. Review
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  8. Zebrafish as an Experimental Model for Human Disease.International journal of molecular sciences · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 14 institutions in 6 countries.

Federica TononDepartment of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy.
Maja CemazarDepartment of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia.ORCID 0000-0002-1418-1928
Urska KamensekDepartment of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia.ORCID 0000-0002-0481-4226
Cristina ZennaroDepartment of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume 447, I-34149 Trieste, Italy.ORCID 0000-0003-4755-1064
Gabriele PozzatoDepartment of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume 447, I-34149 Trieste, Italy.
Sergio CasertaDepartment of Chemical, Materials and Industrial Production Engineering, University of Naples "Federico II", Piazzale V. Tecchio 80, I-80125 Naples, Italy.ORCID 0000-0002-4400-0059
Flora AscioneDepartment of Chemical, Materials and Industrial Production Engineering, University of Naples "Federico II", Piazzale V. Tecchio 80, I-80125 Naples, Italy.
Mario GrassiDepartment of Engineering and Architecture, University of Trieste, Via Valerio 6/A, I-34127 Trieste, Italy.ORCID 0000-0002-3532-3200
Stefano GuidoDepartment of Chemical, Materials and Industrial Production Engineering, University of Naples "Federico II", Piazzale V. Tecchio 80, I-80125 Naples, Italy.ORCID 0000-0002-9247-6852
Cinzia FerrariDepartment of Clinic-Surgical Sciences, Laboratory of Experimental Surgery and Animal Facility, University of Pavia, Via Ferrata 9, I-27100 Pavia, Italy.ORCID 0000-0001-8356-7472
Laura CansolinoDepartment of Clinic-Surgical Sciences, Laboratory of Experimental Surgery and Animal Facility, University of Pavia, Via Ferrata 9, I-27100 Pavia, Italy.ORCID 0000-0002-8330-1532
Francesco TrottaDepartment of General Surgery, Maggiore Hospital, Largo Donatori del Sangue 1, I-26900 Lodi, Italy.
Biljana Grcar KuzmanovDepartment of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia.
Giancarlo ForteInternational Clinical Research Center (ICRC) of St Anne's University Hospital, CZ-65691 Brno, Czech Republic.ORCID 0000-0002-1341-1023
Fabiana MartinoInternational Clinical Research Center (ICRC) of St Anne's University Hospital, CZ-65691 Brno, Czech Republic.
Francesca PerroneDepartment of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy.
Riccardo BombenClinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, Istituto di Ricovero a Cura a Carattere Scientifico IRCCS, 33081 Aviano, Italy.ORCID 0000-0002-8746-9404
Valter GatteiClinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, Istituto di Ricovero a Cura a Carattere Scientifico IRCCS, 33081 Aviano, Italy.
Nicola ElvassoreIndustrial Engineering Department, University of Padova, Via Francesco Marzolo, 9, I-35131 Padova, Italy.
Erminio MuranoNealys SRL, Via Flavia 23/1, I-34148 Trieste, Italy.
Nhung Hai TruongStem Cell Research and Application Laboratory, VNUHCM, University of Science, Ho Chi Minh City 72711, Vietnam.
Michael OlsonDepartment of Chemistry and Biology, X University, MaRS Discovery District, West Tower 661 University Avenue, Toronto, ON M5G 1M1, Canada.ORCID 0000-0003-3428-3507
Rossella FarraDepartment of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy.
Gabriele GrassiDepartment of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy.ORCID 0000-0001-9704-6651
Barbara DapasDepartment of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy.
Ospedale di Cattinara · ITUniversity of Trieste · ITCeinge Biotecnologie Avanzate (Italy) · ITCentro di Riferimento Oncologico · ITInstitute of Oncology Ljubljana · SIInternational Clinical Research Center, St. Anne's University Hospital Brno · CZUniversity of Pavia · ITMaRS · CAOspedale Maggiore · ITUniversity of Cambridge · GBUniversity of Naples Federico II · ITUniversity of Padua · ITUniversity of Primorska · SIVietnam National University Ho Chi Minh City · VN

Funding

Beneficentia Stiftung" of Vaduz Liechtenstein no numberFondazione Benefica Kathleen Foreman Casali of Trieste, Italy no numberItalian Ministry of Foreign Affairs and International Cooperation VN21GR01Progetto HEaD "HIGHER EDUCATION AND DEVELOPMENT" UNITS, Fondo sociale Europeo 2014/2020, Asse 3, Programma specifico 25/15 FP168562300Slovenian Research Agency (ARRS) P3-0003
6 · The paper itself

Abstract

backgroundFor hepatocellular carcinoma (HCC), effective therapeutic approaches are lacking. As aberrant gene methylation is a major contributor to HCC development, demethylating drugs such as 5-azacytidine (5-Aza) have been proposed. As most 5-Aza mechanisms of action are unknown, we investigated its phenotypic/molecular effects.

methods5-Aza effects were examined in the human HCC cell lines JHH-6/HuH-7 and in the rat cell-line N1-S1. We also employed a xenograft mouse model (HuH-7), a zebrafish model (JHH-6), and an orthotopic syngeneic rat model (N1-S1) of HCC.

results5-Aza downregulated cell viability/growth/migration/adhesion by upregulating miR-139-5p, which in turn downregulated ROCK2/cyclin D1/E2F1 and increased p27

conclusionWe demonstrate for the first time that 5-Aza can impair HCC development via upregulation of miR-139-5p, which in turn impairs the ROCK2/cyclin D1/E2F1/cyclin B1 pro-proliferative pathway and the ROCK2/MMP-2 pro-migratory pathway. Thus, we provide novel information about 5-Aza mechanisms of action and deepen the knowledge about the crosstalk among ROCK2/cyclin D1/E2F1/cyclin B1/p27

Indexed as

5-azacytidinecell cycleE2F1hepatocellular carcinomamigrationmiR-139-5pMMP-2ROCK2

Identifiers

PMID35406401
PMCPMC8996928
OpenAlexW4223457247

What OpenQuestion holds

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Registered trials

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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.