Abstract
Purpose: To investigate the effects of pleomorphic adenoma gene like-2 (PLAGL2) on oral squamous cell carcinoma (OSCC).
 Methods: The effects of PLAGL2 on OSCC (CAL-27 and HSC-3) were conducted with loss- and gain-functional assays. Cell proliferation was determined by Cell Counting Kit-8 (CCK8) and colony formation assays. Cell metastasis was assessed by Transwell and wound healing assays. Cell apoptosis of cisplatin-resistant OSCC was evaluated by flow cytometry.
 Results: PLAGL2 expression was significantly elevated in OSCC (p < 0.001), while silencing of PLAGL2 significantly reduced cell proliferation and metastasis of OSCC (p < 0.001). However, overexpression of PLAGL2 promoted OSCC progression through increase in cell proliferation, invasion, and migration. Knockdown of PLAGL2 promoted cell apoptosis of -resistant OSCC, but significantly downregulated protein expression of programmed cell death ligand 1(PD-L1) and zinc finger E-box-binding homeobox 1 (ZEB1) in OSCC (p < 0.01). Moreover, loss of ZEB1 attenuated the PLAGL2 overexpression-induced increase in ZEB1 and PD-L1. Loss of PLAGL2 also reduced in vivo tumor growth of OSCC via regulation of cluster of differentiation 4 protein (CD4) and CD8.
 Conclusion: Knockdown of PLAGL2 exerts anti-tumor effects, improves cisplatin resistance, and enhances anti-tumor immunity in OSCC through suppression of ZEB1/PD-L1 pathway. Thus, PLAGL2 might be a potential therapeutic target for the treatment of OSCC.
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