Evidence map›Paper›PMID 38920644›Full record

ArticleCells2024

Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma.

Hipolito Otoniel Miranda-Roblero, Liliana Faridi Saavedra-Salazar, Marina Galicia-Moreno, Scarlet Arceo-Orozco, Fernando Caloca-Camarena, Ana Sandoval-Rodriguez, Jesús García-Bañuelos, Claudia Frias-Gonzalez, Mónica Almeida-López, Erika Martínez-López and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Noninvasive Evaluation of Prolonged-Release Pirfenidone in Compensated Liver Cirrhosis. ODISEA Study, a Randomised Trial.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Trial
  2. Review
  3. 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

12 authors.

Hipolito Otoniel Miranda-RobleroPrograma de Doctorado en Ciencias en Biología Molecular en Medicina, CUCS, University of Guadalajara, Guadalajara 44340, Mexico.
Liliana Faridi Saavedra-SalazarPrograma de Doctorado en Ciencias en Biología Molecular en Medicina, CUCS, University of Guadalajara, Guadalajara 44340, Mexico.ORCID 0000-0002-0447-4479
Marina Galicia-MorenoInstitute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico.ORCID 0000-0002-7435-1861
Scarlet Arceo-OrozcoInstitute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico.ORCID 0000-0003-4855-622X
Fernando Caloca-CamarenaInstitute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico.ORCID 0000-0003-4033-3814
Ana Sandoval-RodriguezInstitute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico.ORCID 0000-0003-1708-1495
Jesús García-BañuelosInstitute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico.ORCID 0000-0003-3430-9391
Claudia Frias-GonzalezPrograma de Doctorado en Ciencias en Biología Molecular en Medicina, CUCS, University of Guadalajara, Guadalajara 44340, Mexico.
Mónica Almeida-LópezUniversity Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Mexico.
Erika Martínez-LópezInstitute of Translational Nutrigenetics and Nutrigenomics, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico.
Juan Armendariz-BorundaInstitute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico.ORCID 0000-0002-7101-9943
Hugo Christian Monroy-RamirezInstitute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico.ORCID 0000-0001-8891-5317

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Indexed as

Carcinoma, HepatocellularDNA (Cytosine-5-)-Methyltransferase 1DNA MethylationProliferating Cell Nuclear AntigenPyridonesAnimalsDiethylnitrosamineGene Expression Regulation, NeoplasticHep G2 CellsHumansLiver NeoplasmsLiver Neoplasms, ExperimentalMaleRatsRats, Inbred F344DiethylnitrosamineDNA (Cytosine-5-)-Methyltransferase 1DNMT1 protein, humanDnmt1 protein, ratpirfenidoneProliferating Cell Nuclear AntigenPyridonesc-MycDNMT1DNMT3ahepatocellular carcinomaβ-catenin

Identifiers

PMID38920644
PMCPMC11201610

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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.