Ly6D facilitates chemoresistance in laryngeal squamous cell carcinoma through miR-509/β-catenin signaling pathway

Chemotherapy resistance is a major limiting factor in the cure of patients with laryngeal squamous cell carcinoma (LSCC). Lymphocyte antigen 6 superfamily member D (Ly6D) is highly expressed in various tumors, but its role and underlying molecular mechanisms in chemoresistance of LSCC cells remains largely unclear. In this study, we reveal that overexpression of Ly6D facilitates LSCC cell chemoresistance, while Ly6D silencing abolishes this phenotype. Moreover, bioinformatics analysis, PCR array, and functional analysis confirmed that activation of the Wnt/beta-catenin pathway contributes to Ly6D-mediated chemoresistance. The genetic and pharmacological inhibition of beta-catenin compromises chemoresistance mediated by Ly6D overexpression. Mechanistically, Ly6D overexpression significantly attenuates the expression of miR-509-5p, thereby unleashing its target gene CTNNB1 to activate Wnt/beta-catenin pathway and ultimately promote chemoresistance. In contrast, Ly6D augmenting beta-catenin-mediated chemoresistance in LSCC cells were reversed by ectopic expression of miR-509-5p. Furthermore, ectopic expression of miR-509-5p markedly repressed the two other targets, MDM2 and FOXM1. Taken together, these data not only reveal the key role of Ly6D/miR-509-5p/beta-catenin in chemotherapy resistance, but also provide a new strategy for the clinical treatment of refractory LSCC.

Automated summary

Overexpression of Ly6D contributes to chemoresistance in laryngeal squamous cell carcinoma (LSCC) cells, while silencing Ly6D abolishes this phenotype. Activation of the Wnt/beta-catenin pathway is involved in Ly6D-mediated chemoresistance. Ly6D overexpression attenuates the expression of miR-509-5p, which unleashes CTNNB1 to activate Wnt/beta-catenin pathway and promote chemoresistance.