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SFQP regulates CTL mediated cytotoxicity on NSCLC by directly binding to PD-L1 3'UTR
  • Yanming Pan,
  • Yongxia Cheng
Yanming Pan
Mudanjiang Medical University
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Yongxia Cheng
Mudanjiang Medical University

Corresponding Author:mdjtg@mdjmu.edu.cn

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Abstract

Splicing factor proline- and glutamine-rich (SFPQ) can interact with RNAs to regulate gene expression. The function of SFPQ in the immunotherapy of non-small cell lung cancer (NSCLC) is investigated in this study. H1299 and A549 cells were transfected with shSFPQ plasmid. Cell counting kit-8 (CCK-8) and cell clone formation were utilized to detect survival and proliferation. Programmed death-ligand 1 (PD-L1) and SFPQ were detected in NSCLC patients treated with anti-PD-L1 antibody. Dual-luciferase assays, RNA immunoblotting, RNA pull-down, and mRNA stability assay were applied to verify the regulation of PD-L1 with SFPQ. Human peripheral blood mononuclear cells (PBMC)-derived dendritic cells were loaded with irradiated A549 and H1299 cells, which were cultured with autologous CD8+T cells and tumor cells to perform in vitro tumor-specific cytotoxic T cells (CTL) cytotoxicity analysis. SFPQ silencing inhibited the survival and proliferation of H1299 and A549 cells with down-regulated PD-L1 expression. PD-L1 and SFPQ expression were markedly higher in anti-PD-L1 antibody treatment responders compared to non-responders, which showed a positive Pearson correlation (r=0.76, p<0.001). SFPQ up-regulated the relative mRNA and protein expression of PD-L1 by binding to the PD-L1 3’UTR to slow the decay of PD-L1 mRNA. SFPQ silencing promoted the killing effect of CTL on A549 and H1299 cells. SFQP up-regulates PD-L1 expression by binding with PD-L1 3’UTR to slow the decay of PD-L1 mRNA, and SFQP silencing promotes CTL mediated cytotoxicity on NSCLC cells.
15 Jun 2023Submitted to Immunity, Inflammation and Disease
19 Jun 2023Submission Checks Completed
19 Jun 2023Assigned to Editor
19 Jun 2023Review(s) Completed, Editorial Evaluation Pending
27 Jun 2023Reviewer(s) Assigned