Evidence mapPaperPMID 41204108Full record

ArticleCellular & molecular biology letters2025

lncRNA IGFL2-AS1 mediates NSCLC chemoresistance via YBX1-induced HSPA1A/RAP1 activation.

Hongliang Dong, Yunxiu Xia, Jingjing Qi, Cuilan Liu, Fei Wang, Bingjie Cui, Weiwei Chen, Wenwen Lv, Nailiang Zhai, Jiong Deng and 4 more

Abstract read
In one paragraph

Article in Cellular & molecular biology letters, 2025. 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
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

2 citing papers in PubMed.

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4 · The record

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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

14 authors.

Hongliang Dong *Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, 661 Huanghe Second Road, 256600, Binzhou, People's Republic of China.
Yunxiu Xia *Medical Research Center, Binzhou Medical University Hospital, 256600, Binzhou, People's Republic of China.
Jingjing Qi *Faculty of Medicine, Johannes Kepler University Linz, Altenberger Strasse 69, 4040, Linz, Austria.
Cuilan LiuDepartment of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, 661 Huanghe Second Road, 256600, Binzhou, People's Republic of China.
Fei WangDepartment of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, 661 Huanghe Second Road, 256600, Binzhou, People's Republic of China.
Bingjie CuiDepartment of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, 661 Huanghe Second Road, 256600, Binzhou, People's Republic of China.
Weiwei ChenDepartment of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, 661 Huanghe Second Road, 256600, Binzhou, People's Republic of China.
Wenwen LvDepartment of Pharmacy, Binzhou Medical University Hospital, 256600, Binzhou, People's Republic of China.
Nailiang ZhaiDepartment of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, 661 Huanghe Second Road, 256600, Binzhou, People's Republic of China.
Jiong DengDepartment of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, 661 Huanghe Second Road, 256600, Binzhou, People's Republic of China.
Yong YuFaculty of Medicine, Johannes Kepler University Linz, Altenberger Strasse 69, 4040, Linz, Austria.
Fangling NingDepartment of Oncology, Binzhou Medical University Hospital, 256600, Binzhou, People's Republic of China.
Clemens A SchmittFaculty of Medicine, Johannes Kepler University Linz, Altenberger Strasse 69, 4040, Linz, Austria. clemens.schmitt@charite.de.
Jing DuDepartment of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, 661 Huanghe Second Road, 256600, Binzhou, People's Republic of China. djedith@bzmc.edu.cn.

Funding

Funds of Shandong Traditional Chinese Medicine Science and Technology Development Project 2019-0514Ministry of Education "Chunhui" plan international cooperation project HZKY20220459National Natural Science Foundation of China 31900441National Natural Science Foundation of China 81502937National Natural Science Foundation of China 82172565National Natural Science Foundation of China 82373097Natural Science Foundation of Shandong Province WSR2023085Natural Science Foundation of Shandong Province ZR2019MC026Natural Science Foundation of Shandong Province ZR2023QH080Research Foundation of Binzhou Medical University Hospital 2022-01Research Foundation of Binzhou Medical University Hospital BY2022KJ64Research foundation of Johannes Kepler University 2020-2026Tyle Private Foundation BERM16108001
6 · The paper itself

Abstract

backgroundThe development of drug resistance in cancer is associated with multiple malignant properties, including proliferative progression, metastasis, and stemness. Long noncoding RNAs (lncRNAs) reportedly contribute to multidrug resistance in lung cancer. However, functional and mechanistic studies of key lncRNAs associated with lung cancer are lacking.

methodsCandidate lncRNA IGFL2-AS1 and its downstream target, the HSPA1A and RAP1 cascade, were identified using RNA sequencing. In vitro functional assays, including proliferation, clonal formation, Transwell migration, sphere formation, and drug sensitivity test, were conducted to explore the function of the IGFL2-AS1/HSPA1A axis in lung cancer. For in vivo functional validation, subcutaneous implantation and tail vein injection of luciferase-tagged lung cancer cells were performed in mouse models. Moreover, RNA pulldown, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and point/truncated mutations were utilized to dissect the mechanisms underlying the activation of the YBX1-mediated IGFL2-AS1/HSPA1A axis. Pharmacological inhibition of HSPA1A was performed to restore chemotherapy sensitivity and attenuate lung cancer cell metastasis in vivo. Finally, tissue microarray staining was employed to evaluate the expression of the YBX1/IGFL2-AS1/HSPA1A/RAP1 axis in lung cancer specimens and its correlation with prognosis.

resultsIGFL2-AS1, stimulated by C/EBPβ, was aberrantly upregulated in chemoresistant cell lines and lung cancer specimens. IGFL2-AS1 promoted lung cancer proliferation, metastasis, drug resistance, and stemness by upregulating HSPA1A expression both in vitro and in vivo. Mechanistically, IGFL2-AS1 recruited YBX1 to the HSPA1A promoter, facilitating its transcription. Pharmacological inhibition of HSPA1A restored the sensitization of A549 cells resistant to cisplatin and 5-fluorouracil via the downstream RAP1 signaling cascade. Notably, the YBX1/IGFL2-AS1/HSPA1A axis was consistently activated in lung cancer specimens and correlated with poor patient prognosis.

conclusionsThis study demonstrated that the YBX1-modulated IGFL2-AS1/HSPA1A/RAP1 axis is aberrantly activated in lung cancer cells and is associated with unfavorable prognosis, highlighting its potential as a novel therapeutic target in clinical settings.

Indexed as

Carcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmHSP70 Heat-Shock ProteinsLung NeoplasmsRNA, Long NoncodingTelomere-Binding ProteinsY-Box-Binding Protein 1AnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMiceMice, Inbred BALB CMice, NudeHSP70 Heat-Shock ProteinsHSPA1A protein, humanRNA, Long NoncodingTelomere-Binding ProteinsY-Box-Binding Protein 1YBX1 protein, humanDrug resistanceHSPA1AIGFL2-AS1Lung cancerYBX1

Identifiers

PMID41204108
PMCPMC12595904

What Socratic holds

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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 Socratic graph.