Evidence map›Paper›PMID 27494874›Full record

ArticleOncotarget2016

Clock gene Per2 as a controller of liver carcinogenesis.

Ali Mteyrek, Elisabeth Filipski, Catherine Guettier, Alper Okyar, Francis Lévi

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.9field-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

40 citing papers in PubMed, 69 citations in OpenAlex.

  1. Review
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  4. Hepatocellular Carcinoma Around the Clock.Current oncology (Toronto, Ont.) · 2026
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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 4 institutions in 3 countries.

Ali MteyrekINSERM and Paris Sud University, UMRS 995, Team « Cancer Chronotherapy and Postoperative Liver », Campus CNRS, Villejuif F-94807, France.
Elisabeth FilipskiINSERM and Paris Sud University, UMRS 995, Team « Cancer Chronotherapy and Postoperative Liver », Campus CNRS, Villejuif F-94807, France.
Catherine GuettierAssistance Publique-Hopitaux de Paris, Department of Medical Oncology and Laboratory of Anatomy and Pathologic Cytology, Hôpital Paul Brousse, Villejuif F-94800, France.
Alper OkyarIstanbul University Faculty of Pharmacy, Department of Pharmacology, Beyazit TR-34116, Istanbul, Turkey.
Francis LéviINSERM and Paris Sud University, UMRS 995, Team « Cancer Chronotherapy and Postoperative Liver », Campus CNRS, Villejuif F-94807, France.
Université Paris-Sud · FRAssistance Publique – Hôpitaux de Paris · FRInserm · FRIstanbul University · TR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Environmental disruption of molecular clocks promoted liver carcinogenesis and accelerated cancer progression in rodents. We investigated the specific role of clock gene Period 2 (Per2) for liver carcinogenesis and clock-controlled cellular proliferation, genomic instability and inflammation. We assessed liver histopathology, and determined molecular and physiology circadian patterns in mice on chronic diethylnitrosamine (DEN) exposure according to constitutive Per2 mutation. First, we found that Per2m/m liver displayed profound alterations in proliferation gene expression, including c-Myc derepression, phase-advanced Wee1, and arrhythmic Ccnb1 and K-ras mRNA expressions, as well as deregulated inflammation, through arrhythmic liver IL-6 protein concentration, in the absence of any DEN exposure. These changes could then make Per2m/m mice more prone to subsequently develop liver cancers on DEN. Indeed, primary liver cancers were nearly fourfold as frequent in Per2m/m mice as compared to wild-type (WT), 4 months after DEN exposure. The liver molecular clock was severely disrupted throughout the whole carcinogenesis process, including the initiation stage, i.e. within the initial 17 days on DEN. Per2m/m further exhibited increased c-Myc and Ccnb1 mean 24h expressions, lack of P53 response, and arrhythmic ATM, Wee1 and Ccnb1 expressions. DEN-induced tumor related inflammation was further promoted through increased protein concentrations of liver IL-6 and TNF-α as compared to WT during carcinogenesis initiation. Per2 mutation severely deregulated liver gene or protein expressions related to three cancer hallmarks, including uncontrolled proliferation, genomic instability, and tumor promoting inflammation, and accelerated liver carcinogenesis several-fold. Clock gene Per2 acted here as a liver tumor suppressor from initiation to progression.

Indexed as

AnimalsCarcinogenesisCircadian RhythmDiethylnitrosamineInterleukin-6LiverLiver NeoplasmsMaleMiceMice, Inbred C57BLMutationPeriod Circadian ProteinsTumor Necrosis Factor-alphaDiethylnitrosamineInterleukin-6Per2 protein, mousePeriod Circadian ProteinsTumor Necrosis Factor-alphaCell cycle genesCircadian rhythmHepatocellular carcinomaMolecular clockPer2 gene

Identifiers

PMID27494874
PMCPMC5349878
OpenAlexW2503777703

What OpenQuestion 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 OpenQuestion graph.