Abstract
ERP29 gene encodes a chaperone protein critical for protein folding and secretion. Previous study linked ERP29 inhibition to an elevated risk of pharynx squamous cell carcinoma (PSCC) and reduced patients' survival. However, ERP29 role in PSCC progression remains unknown. Here, we investigated ERP29 impact on PSCC progression in cisplatin (CDDP)-sensitive (FaDu and LAU-2063), CDDP-treated (FaDu-CDDP), and CDDP-resistant (FaDu-R) cells. ERP29 silencing decreased necrosis and increased migration in CDDP-sensitive, treated, and resistant cells; and reduced E-cadherin and increased vimentin immunoexpression in CDDP-sensitive 3D-spheroids. During CDDP treatment, ERP29 silencing enhanced proliferation. In CDDP-sensitive cells, ERP29 silencing upregulated genes associated with WNT, MAPK, and PI3K/AKT signaling pathways while downregulating CASP9 expression. During CDDP treatment, ERP29 silencing downregulated MDM2 and CASP9 expression. In CDDP-resistant cells, ERP29 silencing upregulated SOS1, MAPK1, AKT1, ITGAV, and CCNE1, while downregulating KRAS, JUN, MDM2, and CASP9 expression. In addition, inhibition of microRNA miR-4421 increased ERP29 expression and decreased MAPK1, AKT1, and JUN expression in CDDP-sensitive cells, as well as SOS1, MAPK1, AKT1, and ITGAV in CDDP-resistant cells. Lower ERP29 and higher miR-4421 expressions were predictive of poor survival, suggesting a potential therapeutic use for miR-4421 inhibitors. Upon validation, these findings may contribute to targeted therapies for PSCC based on ensuring ERP29 expression.