Cell death & disease, 2019-02, Vol.10 (3), p.156-156, Article 156
2019
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- Autor(en) / Beteiligte
- Titel
- PLOD3 suppression exerts an anti-tumor effect on human lung cancer cells by modulating the PKC-delta signaling pathway
- Ist Teil von
- Cell death & disease, 2019-02, Vol.10 (3), p.156-156, Article 156
- Ort / Verlag
- England: Springer Nature B.V
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Current lung cancer treatments are far from satisfactory; thus, finding novel treatment targets is crucial. We recently identified procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), which is involved in fibrosis and tissue remodeling as a radioresistance-related protein in lung cancer cells; however, its mechanism is unclear. In this study, we designed human PLOD3-specific short interfering (si)RNAs and tested their effects on tumor growth inhibition in vitro and in vivo. PLOD3 knockdown overcame chemoresistance and decreased radioresistance by inducing caspase-3-dependent apoptosis in lung cancer cells. Furthermore, PLOD3 interacted with PKCδ to activate caspase-2,4-dependent apoptosis through ER-stress-induced IRE1α activation and the downstream unfolded-protein response pathway. In a mouse xenograft model, PLOD3 knockdown promoted radiation-induced tumor growth inhibition, without side effects. Moreover, lung cancer patients with high PLOD3 expression showed poorer prognosis than those with low PLOD3 expression upon radiotherapy, suggesting that PLOD3 promotes tumor growth. Therefore, PLOD3 siRNA suppresses radioresistance and chemoresistance by inducing apoptosis and renders PLOD3 as a candidate lung cancer biomarker. PLOD3 gene therapy might enhance the efficacy of radiotherapy or chemotherapy in lung cancer patients.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-4889eISSN: 2041-4889DOI: 10.1038/s41419-019-1405-8Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6377650
- Format
- –
- Schlagworte
- A549 Cells, Animals, Antineoplastic Agents - pharmacology, Apoptosis, Apoptosis - genetics, Biomarkers, Tumor - genetics, Cancer therapies, Carcinogenesis - genetics, Caspase, Caspase-2, Caspase-3, Cell Proliferation - genetics, Chemoresistance, Chemotherapy, DNA Damage - genetics, Drug Resistance, Neoplasm - genetics, Endoplasmic Reticulum Stress - genetics, Fibrosis, Gene Knockdown Techniques, Gene therapy, Growth inhibition, Humans, Ketoglutaric acid, Lung cancer, Lung Neoplasms - metabolism, Lung Neoplasms - pathology, Lysine, Mice, Patients, Procollagen, Procollagen-lysine 5-dioxygenase, Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - genetics, Protein kinase C, Protein Kinase C-delta - metabolism, Radiation therapy, Radioresistance, RNA, Small Interfering - pharmacology, Signal transduction, Signal Transduction - genetics, siRNA, Transfection, Tumor Burden - drug effects, Tumor Burden - radiation effects, Unfolded Protein Response, Xenograft Model Antitumor Assays, Xenografts