Evidence map›Paper›PMID 40665639›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

LncDARS-AS1 Regulates ATP1A1 Stability and Enhances Na

Mingxian Xu, Jiatian Wei, Xiaoyu Feng, Qinkai Zhang, Jian Chen, Xinyue Wang, Xiudan Zhan, Bing Lu, Weitang Guo, Mingzhe Cheng and 3 more

Erratum issuedAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. LncDARS-AS1 Regulates ATP1A1 Stability and Enhances NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Mingxian XuDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.ORCID https://orcid.org/0000-0003-4580-7804
Jiatian WeiCenter for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510000, China.
Xiaoyu FengCenter for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510000, China.
Qinkai ZhangCenter for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510000, China.
Jian ChenCenter for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510000, China.
Xinyue WangCenter for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510000, China.
Xiudan ZhanCenter for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510000, China.
Bing LuMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Weitang GuoDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Mingzhe ChengDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Renxuan HuangDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Shao XuDepartment of Stomatology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, 510630, China.
Changye ZouDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.ORCID https://orcid.org/0009-0007-9214-4181

Funding

National Natural Science Foundation of China 82273413National Natural Science Foundation of China 82473068Science and Technology Planning Project of Guangdong Province 2024A1515013110
6 · The paper itself

Abstract

Osteosarcoma, the most prevalent malignant bone tumour in children and adolescents, exhibits aggressive pulmonary metastasis and poor prognosis. This study identifies LncDARS-AS1 as a key regulator of metastasis via modulation of ATP1A1, the catalytic subunit of Na⁺/K⁺ ATPase (NKA). Transcriptomic analyses, validated by qPCR in 217 osteosarcoma RNA samples, reveal that LncDARS-AS1 is significantly upregulated in metastatic lesions and associated with adverse clinical outcomes. Functional assays confirm that silencing LncDARS-AS1 suppresses osteosarcoma proliferation and metastasis in vitro and in vivo. Mechanistically, LncDARS-AS1 directly binds ATP1A1, preventing its interaction with the UBQLN4 and subsequent proteasomal degradation, thereby enhancing NKA activity. Protein-RNA interactions were validated using ChIRP, mass spectrometry, molecular docking, and molecular dynamics simulations. Functional NKA activity was assessed using ion-sensitive fluorescent indicators and enzymatic assays. Additionally, digoxin, a cardiac glycoside targeting NKA, effectively inhibited tumour growth and metastasis at clinically safe concentrations. These findings uncover a novel LncDARS-AS1/ATP1A1 axis that promotes osteosarcoma metastasis through inhibition of ubiquitin-mediated degradation and provide a rationale for repurposing digoxin in osteosarcoma therapy. ATP1A1 emerges as a promising target for anti-metastatic intervention.

Indexed as

Bone NeoplasmsOsteosarcomaSodium-Potassium-Exchanging ATPaseAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, NudeNeoplasm MetastasisATP1A1 protein, humanSodium-Potassium-Exchanging ATPaseATP1A1digoxinLncDARS‐AS1metastasisNa/K‐ATPaseosteosarcomatumor therapyubiquitination

Identifiers

PMID40665639
PMCPMC12442677

What Socratic 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 Socratic graph.