ArticleJournal of experimental & clinical cancer research : CR2019
Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 191 citations in OpenAlex.
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Advances in the use of exosomes for the diagnosis and treatment of ovarian cancer.World journal of surgical oncology · 2025Review
- The long antisense non-coding RNA HOXA transcript at the distal tip (LncRNA HOTTIP) in health and disease: a comprehensive review and in silico analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Epigenetic Regulation of Immune Responses in Endocrine-Related Cancers and Its Role in Immunotherapy.Cancers · 2025Review
- Role of interleukin-6 in resistance to tumor therapy.Discover oncology · 2025Review
- Neutrophil Dynamics in Response to Cancer Therapies.Cancers · 2025Review
- IL-6 promotes metastasis and EMT of non-small cell lung cancer cells by up-regulating FGL1 via STAT3 pathway.Translational cancer research · 2025Article
- LncRNA HOTTIP modulated by Hedgehog signaling drives colorectal cancer progression by promoting HUWE1-mediated ubiquitin‒proteasome degradation of p53.Cell death & disease · 2025Article
- Recent Advances in Cancer Immunotherapy Aided by Regulatory Non-Coding RNA: A Review.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- A Comprehensive Review of Long Non-Coding RNAs in the Cancer-Immunity Cycle: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Review
- LncRNAs as behind-the-scenes molecules in cancer progression through regulating tumor-associated innate immune system cells.Molecular biology reports · 2025Review
- Metformin induces apoptosis in pituitary-derived folliculostellate cells via the IL-6/ERK pathway.Discover oncology · 2025Article
- HKDC1 promotes ovarian cancer progression through boosting lipid metabolism and immune escape by stabilizing G6PC/G6PC2.Communications biology · 2025Article
- PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.Clinical and experimental medicine · 2025Review
- The role and targeting strategies of non-coding RNAs in immunotherapy resistance in oral squamous cell carcinoma.Frontiers in cell and developmental biology · 2025Review
- Effect of neutrophils on tumor immunity and immunotherapy resistance with underlying mechanisms.Cancer communications (London, England) · 2025Review
- Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.Cancers · 2024Review
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy.Molecular and cellular biochemistry · 2024Review
- Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundLong non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP), has been demonstrated to be a vital biomarker when evaluating the prognosis of multiple cancers. Nevertheless, the potential function of HOTTIP in ovarian cancer (OC), a prevalent cancer among women worldwide, remains elusive. Hence, the current study aimed to elucidate the functional relevance of HOTTIP in the development of OC.
methodsPositive expression of PD-L1 and IL-6 was determined using immunohistochemical staining in the collected OC and normal tissues. The correlation of IL-6 and PD-L1 was analyzed using flow cytometry, Western blot analysis as well as Pearson's correlation coefficient. The interaction among HOTTIP, c-jun and IL-6 was investigated with the use of RIP, ChIP and dual luciferase reporter gene assays. Finally, the effects of HOTTIP on T cell proliferation and infiltration were identified through gain- and loss-of-function studies in vitro and in vivo.
resultsHOTTIP, IL-6 and PD-L1 were all highly expressed in OC tissues. A positive correlation was observed between IL-6 and PD-L1 and that between HOTTIP and IL-6 in OC tissues. HOTTIP was noted to promote the expression of IL-6 by binding to c-jun, which resulted in a promoted PD-L1 expression in neutrophils and immune escape while inhibiting T cell proliferation as well as tumor immunotherapy.
conclusionTaken together, our study unveiled that HOTTIP could promote the secretion of IL-6, and consequently up-regulate the expression of PD-L1 in neutrophils, thus inhibiting the activity of T cells and ultimately accelerating immune escape of OC cells. Our study provides a potential therapeutic strategy by targeting HOTTIP in OC.
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