ArticleCell death & disease2021
Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Prognostic and clinicopathological values of LINC00665 in cancers: a systematic review and China population-based meta-analysis.Clinical and experimental medicine · 2023Pooled it
- The functions of circular RNAs and long noncoding RNAs in cholangiocarcinoma.Discover oncology · 2025Review
- Targeting GPX4 to Induce Ferroptosis Overcomes Chemoresistance Mediated by the PAX8-AS1/GPX4 Axis in Intrahepatic Cholangiocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role and Function of Non-Coding RNAs in Cholangiocarcinoma Invasiveness.Biomedicines · 2025Review
- Biomarkers and Management of Cholangiocarcinoma: Unveiling New Horizons for Precision Therapy.Cancers · 2025Review
- Long Non-Coding RNAs: Key Regulators of Tumor Epithelial/Mesenchymal Plasticity and Cancer Stemness.Cells · 2025Review
- Extracellular vesicles in triple-negative breast cancer: current updates, challenges and future prospects.Frontiers in molecular biosciences · 2025Review
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- The Diagnostic and Prognostic Potentials of Non-Coding RNA in Cholangiocarcinoma.International journal of molecular sciences · 2024Review
- Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma.Cancers · 2024Review
- Non-coding RNA and Drug resistance in cholangiocarcinoma.Non-coding RNA research · 2024Review
- Role of miR-424 in the carcinogenesis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Long noncoding RNA NONHSAT160169.1 promotes resistance via hsa-let-7c-3p/SOX2 axis in gastric cancer.Scientific reports · 2023Article
- Role of the long non-coding RNAs in regulation of Gemcitabine response in tumor cells.Cancer cell international · 2023Review
- LncRNA-NEF suppressed oxaliplatin resistance and epithelial-mesenchymal transition in colorectal cancer through epigenetically inactivating MEK/ERK signaling.Cancer gene therapy · 2023Article
- Serum thrombospondin-1 serves as a novel biomarker and agonist of gemcitabine-based chemotherapy in intrahepatic cholangiocarcinoma.British journal of cancer · 2023Article
- Article
- CSE regulates LINC000665/XBP-1 in the progress of pulmonary fibrosis.Tobacco induced diseases · 2023Article
- Role of the PP2A Pathway in Cholangiocarcinoma: State of the Art and Future Perspectives.Cancers · 2022Article
- Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665 (LINC00665) were found to rank the top 10 upregulated lncRNAs in our study, and high LINC00665 expression was closely associated with poor prognosis and chemoresistance of CCA patients. Silencing LINC00665 in gemcitabine resistant CCA cells impaired gemcitabine tolerance, while enforced LINC00665 expression increased gemcitabine resistance of sensitive CCA cells. The gemcitabine resistant CCA cells showed increased EMT and stemness properties, and silencing LINC00665 suppressed sphere formation, migration, invasion and expression of EMT and stemness markers. In addition, Wnt/β-Catenin signaling was activated in gemcitabine resistant CCA cells, but LINC00665 knockdown suppressed Wnt/β-Catenin activation. B-cell CLL/lymphoma 9-like (BCL9L), the nucleus transcriptional regulators of Wnt/β-Catenin signaling, plays a key role in the nucleus translocation of β-Catenin and promotes β-Catenin-dependent transcription. In our study, we found that LINC00665 regulated BCL9L expression by acting as a molecular sponge for miR-424-5p. Moreover, silencing BCL9L or miR-424-5p overexpression suppressed gemcitabine resistance, EMT, stemness and Wnt/β-Catenin activation in resistant CCA cells. In conclusion, our results disclosed the important role of LINC00665 in gemcitabine resistance of CCA cells, and provided a new biomarker or therapeutic target for CCA treament.
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