Evidence map›Paper›PMID 28692045›Full record

ArticleOncogene2017

Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation.

T Nakatsuka, K Tateishi, Y Kudo, K Yamamoto, H Nakagawa, H Fujiwara, R Takahashi, K Miyabayashi, Y Asaoka, Y Tanaka and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Histone methylation in pre-cancerous liver diseases and hepatocellular carcinoma: recent overview.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. microRNA-155-3p attenuates intervertebral disc degeneration via inhibition of KDM3A and HIF1α.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021
    Article
  14. Article
  15. Article
  16. Review
  17. The perplexity of targeting genetic alterations in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2020
    Article
  18. Review
  19. Article
  20. 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

19 authors at 4 institutions in 1 country.

T NakatsukaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
K TateishiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Y KudoDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
K YamamotoDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
H NakagawaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
H FujiwaraDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
R TakahashiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
K MiyabayashiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Y AsaokaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Y TanakaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
H IjichiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Y HirataDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
M OtsukaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.ORCID 0000-0003-2869-2881
M KatoCellular Memory Laboratory, RIKEN Advanced Science Institute, Wako-shi, Saitama, Japan.
J SakaiDivision of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo, Japan.
M TachibanaDepartment of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima-shi, Tokushima, Japan.
H AburataniGenome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo, Japan.
Y ShinkaiCellular Memory Laboratory, RIKEN Advanced Science Institute, Wako-shi, Saitama, Japan.
K KoikeDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
The University of Tokyo · JPRIKEN Advanced Science Institute · JPTokushima University · JPTokyo Institute of Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation. Particularly, the expression of Cd44, a liver cancer stem marker, was regulated by AP-1 in a Kdm3a-dependent manner. We identified Cd44-positive hepatocytes with epithelial-mesenchymal transition-related expression profiles in the Pik3ca Tg liver and confirmed their in vivo tumorigenic capacity. Notably, the number and tumor-initiating capacity of Cd44-positive hepatocytes were governed by Kdm3a. As a mechanism in Kdm3a-dependent AP-1 transcription, Kdm3a recruited c-Jun to the AP-1 binding sites of Cd44, Mmp7 and Pdgfrb without affecting c-Jun expression. Moreover, Brg1, a component of the SWI/SNF chromatin remodeling complex, interacted with c-Jun in a Kdm3a-dependent manner and was bound to the AP-1 binding site of these genes. Finally, KDM3A and c-JUN were co-expressed in 33% of human premalignant lesions with PI3K activation. Our data suggest a critical role for KDM3A in the PI3K/AP-1 oncogenic axis and propose a novel strategy for inhibition of KDM3A against liver tumor development under PI3K pathway activation.

Indexed as

AnimalsCarcinogenesisCarcinoma, HepatocellularCell Line, TumorClass I Phosphatidylinositol 3-KinasesEpigenesis, GeneticHumansJumonji Domain-Containing Histone DemethylasesLiver NeoplasmsLiver Neoplasms, ExperimentalMaleMiceMice, KnockoutMice, TransgenicPhosphatidylinositol 3-KinasesPhosphorylationClass I Phosphatidylinositol 3-KinasesJumonji Domain-Containing Histone DemethylasesKDM3A protein, humanKdm3a protein, mousePhosphatidylinositol 3-KinasesPIK3CA protein, humanPik3ca protein, mouseTranscription Factor AP-1

Identifiers

PMID28692045
OpenAlexW2734424944

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.