Evidence map›Paper›PMID 40011917›Full record

ArticleMolecular cancer2025

Hsa_circ_0125356 promotes gemcitabine resistance by modulating WNT canonical and non-canonical pathways via miR-582-5p/FGF9 axis in non-small cell lung cancer.

Xinyue Du, Weijie Luo, Hongwu Li, Qi Gu, Ping Huang, Cheng Wang, Na Li, Fanglan Liu, Chunhua Xia

Abstract read
In one paragraph

Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Translational lung cancer research · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Circular RNAs: from transcriptional noise to engineered therapeutics.Frontiers in epigenetics and epigenomics · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. 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

9 authors.

Xinyue Du *School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China.
Weijie Luo *School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China.
Hongwu LiSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China.
Qi GuSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China.
Ping HuangSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China.
Cheng WangSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China.
Na LiSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China.
Fanglan LiuSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China. liufanglan@ncu.edu.cn.
Chunhua XiaSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, P. R. China. xch720917@ncu.edu.cn.

Funding

National Natural Science Foundation of China No. 82160708National Natural Science Foundation of China No. 82260717
6 · The paper itself

Abstract

backgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality worldwide. The prognosis of patients has been significantly improved by chemotherapy, but acquired drug resistance remains a major obstacle to NSCLC treatment. Circular RNAs (circRNAs), which act as miRNA or protein sponges, are critically associated with the development and chemotherapy resistance of NSCLC.

methodsCircRNA sequencing was performed to analyze the differential expression of circRNAs between A549 and A549-GR cells. Chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) technologies were used to detect the expression of hsa_circ_0125356, miR-582-5p,and FGF9 in NSCLC tissues and para-carcinoma tissues. Fluorescence in situ hybridization (FISH), dual-luciferase reporter assays and RNA immunoprecipitation (RIP) were conducted to evaluate the expression and regulation of hsa_circ_0125356, miR-582-5p, and FGF9. Furthermore, the regulation of hsa_circ_0125356/miR-582-5p/FGF9 on gemcitabine sensitivity was confirmed by TUNEL, Transwell, EdU, CCK8 and immunohistochemistry.

resultsWe identified a novel hsa_circ_0125356 as a therapeutic target against gemcitabine resistance. Hsa_circ_0125356 was significantly elevated in clinical samples of patients with NSCLC. Moreover, hsa_circ_0125356 overexpression promoted gemcitabine resistance to NSCLC by upregulating FGF9 via sponging miR-582-5p in vivo and in vitro. Notably, WNT canonical (ERK/GSK3β/β-catenin) and non-canonical (Daam1/RhoA/ROCK2) signaling pathways were activated due to hsa_circ_0125356 acting as an endogenous miR-582-5p sponge to regulate the expression of FGF9, and thereby enhancing gemcitabine resistance via promoting DNA damage repair and inhibition of apoptosis. The results were further confirmed by two small molecule antagonists, WAY 316606 and XAV-939,which could inhibit the activation of WNT signaling pathway induced by hsa_circ_0125356.

conclusionWe first demonstrated that hsa_circ_0125356 was significantly upregulated and served as a biomarker for gemcitabine resistance in NSCLC by sponging miR-582-5p/FGF9 axis to regulate the WNT canonical and non-canonical signaling pathways, which provided a new direction for identification of therapeutic targets for the treatment of gemcitabine resistance of NSCLC.

Indexed as

Carcinoma, Non-Small-Cell LungDeoxycytidineDrug Resistance, NeoplasmFibroblast Growth Factor 9Lung NeoplasmsMicroRNAsRNA, CircularWnt Signaling PathwayAnimalsAntimetabolites, AntineoplasticApoptosisCell Line, TumorCell ProliferationFemaleGemcitabineGene Expression Regulation, NeoplasticAntimetabolites, AntineoplasticDeoxycytidineFGF9 protein, humanFibroblast Growth Factor 9GemcitabineMicroRNAsRNA, CircularCircRNAsFGF9Gemcitabine resistanceMiR-582-5pNSCLCWNT canonical and non-canonical signaling pathways

Identifiers

PMID40011917
PMCPMC11866803

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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.