Evidence map›Paper›PMID 36864422›Full record

ArticleCell communication and signaling : CCS2023

KCNJ2/HIF1α positive-feedback loop promotes the metastasis of osteosarcoma.

Mao Shen, Runsang Pan, Shan Lei, Lu Zhang, Changhua Zhou, Zhirui Zeng, Yingjie Nie, Xiaobin Tian

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.8field-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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Journal of extracellular vesicles · 2025
    Article
  5. Article
  6. Article
  7. Lipid Peroxidation-Related Redox Signaling in Osteosarcoma.International journal of molecular sciences · 2024
    Review
  8. 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

8 authors at 3 institutions in 1 country.

Mao Shen *Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Runsang Pan *School of Basic Medicine, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Shan Lei *School of Basic Medicine, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Lu ZhangDepartment of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Changhua ZhouSchool of Clinical Medicine, Guizhou Medical University, Guiyang, 550009, Guizhou, China.
Zhirui ZengSchool of Basic Medicine, Guizhou Medical University, Guiyang, 550009, Guizhou, China. 987963481@qq.com.
Yingjie NieThe Central Laboratory, Guizhou Provincial Peoples Hospital, Guiyang, 550009, Guizhou, China. nienyj@hotmail.com.
Xiaobin TianDepartment of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550009, Guizhou, China. txb6@vip.163.com.
Guiyang Medical University · CNAffiliated Hospital of Guizhou Medical University · CNGuizhou Provincial People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEarly metastasis is a hallmark of osteosarcoma (OS), a highly common type of malignant tumor. Members of the potassium inwardly rectifying channel family exert oncogenic effects in various cancers. However, the role of the potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) in OS is unclear.

methodsThe expression of KCNJ2 in OS tissues and cell lines was measured using bioinformatic analysis, immunohistochemistry, and western blotting. Wound-healing assays, Transwell assays, and lung metastasis models were used to analyze the effects of KCNJ2 on mobility of OS cells. The molecular mechanisms linking KCNJ2 and HIF1α in OS were explored by mass spectrometry analysis, immunoprecipitation, ubiquitination detection, and chromatin-immunoprecipitation quantitative real-time polymerase chain reaction.

resultsKCNJ2 was found to be overexpressed in advanced-stage OS tissues, as well as in cells with high metastatic potential. High expression of KCNJ2 was associated with a shorter survival rate of OS patients. KCNJ2-inhibition repressed the metastasis of OS cells, whereas KCNJ2-elevation induced the opposite effects. Mechanistically, KCNJ2 binds to HIF1α and inhibits its ubiquitination, thus increasing the expression of HIF1α. Interestingly, HIF1α binds directly to the KCNJ2 promoter and increases its transcription under hypoxic conditions.

conclusionTaken together, our results indicated that a KCNJ2/HIF1α positive feedback loop exists in OS tissues, which significantly promotes OS cell metastasis. This evidence may contribute to the diagnosis and treatment of OS. Video Abstract.

Indexed as

Bone NeoplasmsOsteosarcomaPotassium Channels, Inwardly RectifyingBiological AssayCell LineFeedbackHumansKCNJ2 protein, humanPotassium Channels, Inwardly RectifyingHIF1αKCNJ2MetastasisOsteosarcoma

Identifiers

PMID36864422
PMCPMC9979522
OpenAlexW4322770175

What OpenQuestion holds

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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.