Evidence map›Paper›PMID 34667224›Full record

ArticleScientific reports2021

K15 promoter-driven enforced expression of NKIRAS exhibits tumor suppressive activity against the development of DMBA/TPA-induced skin tumors.

Kenji Tago, Satoshi Ohta, Chihiro Aoki-Ohmura, Megumi Funakoshi-Tago, Miho Sashikawa, Takeshi Matsui, Yuki Miyamoto, Taeko Wada, Tomoyuki Oshio, Mayumi Komine and 5 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 56% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. MIR4726Cell communication and signaling : CCS · 2025
    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

15 authors at 5 institutions in 1 country.

Kenji TagoDivision of Structural Biochemistry, Department of Biochemistry, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan. ktago@jichi.ac.jp.
Satoshi OhtaDivision of Structural Biochemistry, Department of Biochemistry, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Chihiro Aoki-OhmuraDivision of Structural Biochemistry, Department of Biochemistry, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Megumi Funakoshi-TagoDivision of Hygienic Chemistry, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
Miho SashikawaDepartment of Dermatology, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Takeshi MatsuiLaboratory for Evolutionary Cell Biology of the Skin, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo, 192-0982, Japan.
Yuki MiyamotoDepartment of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo, 157-8535, Japan.
Taeko WadaDivision of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Tomoyuki OshioDepartment of Dermatology, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Mayumi KomineDepartment of Dermatology, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Jitsuhiro MatsugiDivision of Structural Biochemistry, Department of Biochemistry, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Yusuke FurukawaDivision of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Mamitaro OhtsukiDepartment of Dermatology, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Junji YamauchiDepartment of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo, 157-8535, Japan.
Ken YanagisawaDivision of Structural Biochemistry, Department of Biochemistry, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Jichi Medical University · JPKeio University · JPNational Center For Child Health and Development · JPTokyo University of Pharmacy and Life Sciences · JPTokyo University of Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

NKIRAS1 and NKIRAS2 (also called as κB-Ras) were identified as members of the atypical RAS family that suppress the transcription factor NF-κB. However, their function in carcinogenesis is still controversial. To clarify how NKIRAS acts on cellular transformation, we generated transgenic mice in which NKIRAS2 was forcibly expressed using a cytokeratin 15 (K15) promoter, which is mainly activated in follicle bulge cells. The ectopic expression of NKIRAS2 was mainly detected in follicle bulges of transgenic mice with NKIRAS2 but not in wild type mice. K15 promoter-driven expression of NKIRAS2 failed to affect the development of epidermis, which was evaluated using the expression of K10, K14, K15 and filaggrin. However, K15 promoter-driven expression of NKIRAS2 effectively suppressed the development of skin tumors induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA). This observation suggested that NKIRAS seemed to function as a tumor suppressor in follicle bulges. However, in the case of oncogenic HRAS-driven cellular transformation of murine fibroblasts, knockdown of NKIRAS2 expression drastically suppressed HRAS-mutant-provoked cellular transformation, suggesting that NKIRAS2 was required for the cellular transformation of murine fibroblasts. Furthermore, moderate enforced expression of NKIRAS2 augmented oncogenic HRAS-provoked cellular transformation, whereas an excess NKIRAS2 expression converted its functional role into a tumor suppressive phenotype, suggesting that NKIRAS seemed to exhibit a biphasic bell-shaped enhancing effect on HRAS-mutant-provoked oncogenic activity. Taken together, the functional role of NKIRAS in carcinogenesis is most likely determined by not only cellular context but also its expression level.

Indexed as

AnimalsCarcinogenesisCarrier ProteinsCell Transformation, NeoplasticEpidermisFilaggrin ProteinsGene ExpressionGenes, rasMaleMiceMice, Inbred C57BLMice, TransgenicNF-kappa BPromoter Regions, Geneticras ProteinsSkin NeoplasmsCarrier ProteinsFilaggrin ProteinsNF-kappa BNKIRAS1 protein, humanras Proteins

Identifiers

PMID34667224
PMCPMC8526694
OpenAlexW3206478750

What OpenQuestion holds

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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.