The impact ofERP29on the progression of pharyngeal squamous cell carcinoma

Abstract

AbstractObjectivesWe investigatedERP29gene role on pharynx squamous cell carcinoma (PSCC) progression in cisplatin (CDDP)-sensitive (FaDu and LAU-2063), CDDP-treated (FaDu-CDDP), and CDDP-resistant (FaDu-R) cells.Materials and MethodsCells, modified to induceERP29overexpression or silencing, were mainly submitted to cell proliferation, necrosis, and migration assay. E-cadherin immunoexpression was assessed in three-dimensional spheroids. WNT, MAPK, and PI3K/AKT pathways genes’ expression were identified by PCR array and validated by qPCR. The influence of microRNA miR-4421 inhibitor onERP29expression, and its target genes, were quantified by qPCR.ResultsERP29silencing especially decreased necrotic cell death and increased migration in CDDP-sensitive, treated, and resistant cells, and decreased E-cadherin immunoexpression in CDDP-sensitive three-dimensional-spheroids. During CDDP treatment,ERP29silencing increased cell proliferation. In CDDP-sensitive cells,ERP29silencing increased the expression of several genes involved in WNT, MAPK, and PI3K/AKT pathways and decreasedCASP9expression. During CDDP treatment,ERP29silencing decreasedMDM2andCASP9expression. In CDDP-resistant cells,ERP29silencing increasedSOS1,MAPK1,AKT1,ITGAV, andCCNE1; and decreasedKRAS,JUN,MDM2, andCASP9expression. In addition, miR-4421 inhibition increasedERP29expression and decreasedMAPK1,AKT1,andJUNexpression in CDDP-sensitive cells; andSOS1,MAPK1,AKT1,andITGAVin CDDP-resistant cells, suggesting a potential therapeutic use for miR-4421 inhibitor.ConclusionsERP29silencing seems to decrease necrosis and increase migration of PSCC cells by modulating genes enrolled in WNT, MAPK, and PI3K/AKT pathways. Once validated, our data may enable target therapy development based on ensuringERP29expression that could benefit patients with CDDP-sensitive and resistant tumors.