ArticleExperimental and therapeutic medicine2017
PCSK9 regulates apoptosis in human lung adenocarcinoma A549 cells via endoplasmic reticulum stress and mitochondrial signaling pathways.
Article in Experimental and therapeutic medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 66 citations in OpenAlex.
- Role of PCSK9 in hallmarks of cancer: From mechanisms to interventions (Review).Oncology letters · 2026Review
- Revisiting the Lipid-Cancer Axis: PCSK9, ANGPTL3, and CETP as Emerging Biomarkers and Therapeutic Targets in Oncology.Biomolecules · 2026Review
- Association of PCSK9 inhibitors versus statins with cancer incidence: a target trial emulation.Cardio-oncology (London, England) · 2026Article
- A narrative review of PCSK9 inhibitors: from evolocumab to novel discoveries.Frontiers in pharmacology · 2026Review
- PCSK9 in Cancer: Biological Mechanisms and Implications for Therapeutic Resistance.Biomolecules · 2025Review
- LDHA associated with telomerase-related genes promotes tumorigenesis and progression of lung adenocarcinoma.Scientific reports · 2025Article
- A Pre-Clinical Study on the Use of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor PEP 2-8 to Mitigate Ischemic Injury in a Rat Marginal Donor Model.International journal of molecular sciences · 2025Article
- PCSK9 Promotes the Malignancy of Triple-negative Breast Cancer Cells by Reducing Cholesterol Levels at the Plasma Membrane to Activate EGFR and HER3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inclisiran in Cardiovascular Health: A Review of Mechanisms, Efficacy, and Future Prospects.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- PCSK9 Manipulates Lipid Metabolism and the Immune Microenvironment in Cancer.OncoTargets and therapy · 2025Review
- PCSK9 in T-cell function and the immune response.Biomarker research · 2024Review
- Integrated bioinformatics analysis identifies PCSK9 as a prognosticator correlated with lipid metabolism in pancreatic adenocarcinoma.World journal of surgical oncology · 2024Article
- Contrasting effects of intracellular and extracellular human PCSK9 on inflammation, lipid alteration and cell death.Communications biology · 2024Article
- The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies.Metabolites · 2024Review
- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Causal relationship between lipid-lowering drugs and ovarian cancer, cervical cancer: a drug target mendelian randomization study.BMC cancer · 2024Article
- Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy.BMC cancer · 2024Article
- Cancer and Cardiovascular Disease: The Conjoined Twins.Cancers · 2024Review
- Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall.International journal of molecular sciences · 2024Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the subtilisin family of PCs that encodes a neural apoptosis-regulated convertase 1. However, the precise role of PCSK9 in lung cancer cell apoptosis has remained elusive. In the present study, A549 human lung adenocarcinoma cells were transfected with PCSK9 small interfering (si)RNA to investigate the underlying mechanisms of apoptosis. The results indicated that PCSK9 siRNA exhibited anti-tumor activity by inducing apoptosis as determined by a Cell Counting Kit-8 and Hoechst staining analysis. In addition, PCSK9 siRNA significantly increased apoptosis of A549 cells in part via activation of caspase-3 and downregulation of the anti-apoptotic proteins survivin and X-linked inhibitor of apoptosis protein. Moreover, the results demonstrated that perturbations in the mitochondrial membrane were associated with the deregulation of the Bax/Bcl-2 ratio, which led to the release of cytochrome c after PCSK9 siRNA transfection. In addition, PCSK9 siRNA also induced endoplasmic reticulum stress (ERS) by increasing the levels of 78 kDa glucose-regulated protein (GRP78), GRP94, phosphorylated protein kinase R-like ER kinase and phosphorylated eukaryotic initiation factor 2α. Therefore, these results demonstrated that PCSK9 siRNA may exert its anti-tumor activity through inducing mitochondrial dysfunction and ERS-associated cell death in A549 cells.
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