Evidence map›Paper›PMID 25822025›Full record

ArticleThe Journal of clinical investigation2015

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling.

Jinchang Lu, Guohui Song, Qinglian Tang, Changye Zou, Feng Han, Zhiqiang Zhao, Bicheng Yong, Junqiang Yin, Huaiyuan Xu, Xianbiao Xie and 5 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

75 citing papers in PubMed, 123 citations in OpenAlex.

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15 more citing papers are in PubMed but not listed here.

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 2 countries.

Jinchang Lu
Guohui Song
Qinglian Tang
Changye Zou
Feng Han
Zhiqiang Zhao
Bicheng Yong
Junqiang Yin
Huaiyuan Xu
Xianbiao Xie
Tiebang Kang
YingLee Lam
Huiling Yang
Jingnan Shen
Jin Wang
The First Affiliated Hospital, Sun Yat-sen University · CNSun Yat-sen University · CNUniversity of Hong Kong · HKGuangdong Province Women and Children Hospital · CNState Key Laboratory of Oncology in South China

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteosarcoma is a common malignant bone tumor with a propensity to metastasize to the lungs. Epigenetic abnormalities have been demonstrated to underlie osteosarcoma development; however, the epigenetic mechanisms that are involved in metastasis are not yet clear. Here, we analyzed 2 syngeneic primary human osteosarcoma cell lines that exhibit disparate metastatic potential for differences in epigenetic modifications and expression. Using methylated DNA immunoprecipitation (MeDIP) and microarray expression analysis to screen for metastasis-associated genes, we identified Iroquois homeobox 1 (IRX1). In both human osteosarcoma cell lines and clinical osteosarcoma tissues, IRX1 overexpression was strongly associated with hypomethylation of its own promoter. Furthermore, experimental modulation of IRX1 in osteosarcoma cell lines profoundly altered metastatic activity, including migration, invasion, and resistance to anoikis in vitro, and influenced lung metastasis in murine models. These prometastatic effects of IRX1 were mediated by upregulation of CXCL14/NF-κB signaling. In serum from osteosarcoma patients, the presence of IRX1 hypomethylation in circulating tumor DNA reduced lung metastasis-free survival. Together, these results identify IRX1 as a prometastatic gene, implicate IRX1 hypomethylation as a potential molecular marker for lung metastasis, and suggest that epigenetic reversion of IRX1 activation may be beneficial for controlling osteosarcoma metastasis.

Indexed as

DNA MethylationAnimalsAnoikisBase SequenceBone NeoplasmsCell Line, TumorCell MovementChemokines, CXCFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Screening AssaysHomeodomain ProteinsHumansLung NeoplasmsMiceChemokines, CXCCXCL14 protein, humanHomeodomain ProteinsIRX1 protein, humanNeoplasm ProteinsNF-kappa BRNA, MessengerRNA, NeoplasmTranscription Factors

Identifiers

PMID25822025
PMCPMC4463198
OpenAlexW2022674844

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.