Iranian Journal of Immunology (Sep 2023)
SPIB Knockdown Inhibits the Immune Escape of Ovarian Cancer Cells by Reducing PD-L1 (CD274) Expression and Inactivating the JAK/STAT Pathway
Abstract
Background: Spi-B transcription factor (SPIB) is an E-twenty-six (ETS) transcription factor associated with tumor immunity.Objective: To investigate the functions and mechanisms of SPIB in ovarian cancer (OC) cells.Methods: Cell proliferation, apoptosis, migration, and invasion were determined using colony formation, EdU, flow cytometry, and transwell assays, respectively. The binding sites of programmed death-ligand 1 (PD-L1) and SPIB were predicted using the JASPAR database and verified using the ChIP and luciferase reporter assays.Results: SPIB knockdown inhibited OC cell proliferation, migration, and invasion, and significantly boosted apoptosis (p<0.05). SPIB directly enhanced PD-L1 transcription in OVCAR-3 and SKOV3 cells (p<0.05). Importantly, the JAK/STAT pathway was markedly inactivated in OC cells upon SPIB knockdown. SPIB knockdown markedly decreased JAK2 and STAT1 phosphorylation in OVCAR-3 and SKOV3 cells (p<0.05).Conclusion: These data indicate that SPIB knockdown inhibits OC cell progression by downregulating PD-L1 and inactivating the JAK/STAT pathway.
Keywords