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.
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.
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Who cites it
12 citing papers in PubMed.
- Identification of Candidate mRNA and miRNA Molecules Associated with Tuberculosis Through Preliminary Analysis and Validation Using Clinical Samples.International journal of molecular sciences · 2026Article
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- Circular RNA hsa_circ_0001829 promotes pancreatic ductal adenocarcinoma through miR-7113-3p/DTX4 axis.World journal of surgical oncology · 2026Article
- Oncolytic adenovirus encoding a TGF-β inhibitor synergizes with PD-1 blockade to potentiate NK cell cytotoxicity against NSCLC.Frontiers in immunology · 2026Article
- Decoding the role of non-coding RNAs in HNSCC radioresistance: molecular mechanisms and clinical implications.Frontiers in oncology · 2026Review
- Circular RNAs: from transcriptional noise to engineered therapeutics.Frontiers in epigenetics and epigenomics · 2026Review
- DCST1-AS1 promotes renal cell carcinoma progression via regulating the miR-582-5p/HMGB2 axis.Journal of translational medicine · 2025Article
- Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance.Molecular cancer · 2025Review
- CCDC58 drives lung adenocarcinoma progression via the PI3K/AKT signaling pathway.Frontiers in oncology · 2025Article
- The potential of targeting autophagy-related non-coding RNAs in the treatment of lung cancer.Frontiers in pharmacology · 2025Review
- Engineered exosomes: a promising design platform for overcoming cancer therapy resistance.Frontiers in cell and developmental biology · 2025Review
- Prognostic model of ubiquitination-related genes in ovarian cancer based on transcriptomic analysis and experimental validation.Frontiers in immunology · 2025Article
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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.
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