ArticleJournal of experimental & clinical cancer research : CR2021
Hypoxia-sensitive long noncoding RNA CASC15 promotes lung tumorigenesis by regulating the SOX4/β-catenin axis.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Long non-coding RNAs in B-cell acute lymphoblastic leukemia: Disease implication, challenges and therapeutic opportunities.Non-coding RNA research · 2026Review
- Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review).Oncology reports · 2026Review
- Comparative Analysis of Differentially Expressed Long Non-Coding RNA in Pre- and Postmenopausal Fibroids.International journal of molecular sciences · 2025Article
- SOX4 as a Key Oncogene Driving Tumor Invasion in Retinoblastoma.Investigative ophthalmology & visual science · 2025Article
- SOX4-BMI1 axis promotes non-small cell lung cancer progression and facilitates angiogenesis by suppressing ZNF24.Cell death & disease · 2024Article
- Prohibitin 2 orchestrates long noncoding RNA and gene transcription to accelerate tumorigenesis.Nature communications · 2024Article
- Crosstalk between lncRNAs and Wnt/β-catenin signaling pathways in lung cancers: From cancer progression to therapeutic response.Non-coding RNA research · 2024Review
- DeepGRNCS: deep learning-based framework for jointly inferring gene regulatory networks across cell subpopulations.Briefings in bioinformatics · 2024Article
- The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression.Frontiers in immunology · 2024Article
- LINC02159 promotes non-small cell lung cancer progression via ALYREF/YAP1 signaling.Molecular cancer · 2023Article
- Long non‑coding RNAs as potential therapeutic targets in non‑small cell lung cancer (Review).International journal of molecular medicine · 2023Review
- New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.Seminars in cancer biology · 2023Review
- VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization.International journal of oncology · 2023Article
- Identification of endoplasmic reticulum stress-related lncRNAs in lung adenocarcinoma by bioinformatics and experimental validation.Annals of medicine · 2023Article
- Identifying Genetic Biomarkers Predicting Response to Anti-Vascular Endothelial Growth Factor Injections in Diabetic Macular Edema.International journal of molecular sciences · 2022Article
- Long noncoding RNA regulatory factor X3- antisense RNA 1 promotes non-small cell lung cancer via the microRNA-577/signal transducer and activator of transcription 3 axis.Bioengineered · 2022Article
- Subpopulations of cancer-associated fibroblasts link the prognosis and metabolic features of pancreatic ductal adenocarcinoma.Annals of translational medicine · 2022Article
- LncRNA CASC15, MiR-23b Cluster and SMAD3 form a Novel Positive Feedback Loop to promote Epithelial-Mesenchymal Transition and Metastasis in Ovarian Cancer.International journal of biological sciences · 2022Article
- Integrated analysis of hypoxia-associated lncRNA signature to predict prognosis and immune microenvironment of lung adenocarcinoma patients.Bioengineered · 2021Article
- Identification of Prognostic Model Based on Immune-Related LncRNAs in Stage I-III Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAccumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles in enabling malignant cells to survive under hypoxic stress. However, the molecular crosstalk between lncRNAs and hypoxia signaling cascades in non-small cell lung cancer (NSCLC) remains largely elusive.
methodsFirstly, we identified differentially expressed lncRNA cancer susceptibility candidate 15 (CASC15) as associated with NSCLC based on bioinformatic data. The clinical significance of CASC15 in lung cancer was investigated by Kaplan-Meier survival analysis. Then, we modulated CASC15 expression in NSCLC cell lines by RNAi. CCK-8 and transwell assays were carried out to examine the effects of CASC15 on proliferation and migration of NSCLC cells. Upstream activator and downstream targets of CASC15 were validated by luciferase reporter assay, qRT-PCR, Western blotting, and chromatin immunoprecipitation (ChIP). Lastly, RNA in situ hybridization (RNA-ISH) and immunohistochemistry (IHC) were performed to confirm the genetic relationships between CASC15 and related genes in clinical samples.
resultsCASC15 was highly expressed in NSCLC tissues and closely associated with poor prognosis. Loss-of-function analysis demonstrated that CASC15 was essential for NSCLC cell migration and growth. Mechanistic study revealed that CASC15 was transcriptionally activated by hypoxia signaling in NSCLC cells. Further analysis showed that hypoxia-induced CASC15 transactivation was mainly dependent on hypoxia-inducible factor 1α (HIF-1α) and hypoxia response elements (HREs) located in CASC15 promoter. CASC15 promotes the expression of its chromosomally nearby gene, SOX4. Then SOX4 functions to stabilize β-catenin protein, thereby enhancing the proliferation and migration of NSCLC cells. HIF-1α/CASC15/SOX4/β-catenin pathway was activated in a substantial subset of NSCLC patients.
conclusionsHIF-1α/CASC15/SOX4/β-catenin axis plays an essential role in the development and progression of NSCLC. The present work provides new evidence that lncRNA CASC15 holds great promise to be used as novel biomarkers for NSCLC. Blocking the HIF-1α/CASC15/SOX4/β-catenin axis can serve as a potential therapeutic strategy for treating NSCLC.
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