PMID- 37293155 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230612 IS - 2156-6976 (Print) IS - 2156-6976 (Electronic) IS - 2156-6976 (Linking) VI - 13 IP - 5 DP - 2023 TI - Ly6D facilitates chemoresistance in laryngeal squamous cell carcinoma through miR-509/beta-catenin signaling pathway. PG - 2155-2171 AB - 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. CI - AJCR Copyright (c) 2023. FAU - Wang, Jue AU - Wang J AD - Department of Prosthodontics, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi, China. AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi, China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer Taiyuan 030001, Shanxi, China. AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer Taiyuan 030001, Shanxi, China. FAU - Sheng, Nanning AU - Sheng N AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi, China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer Taiyuan 030001, Shanxi, China. AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer Taiyuan 030001, Shanxi, China. AD - Faculty of Stomatology, Shanxi Medical University Taiyuan 030001, Shanxi, China. FAU - Li, Ying AU - Li Y AD - Department of Prosthodontics, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi, China. FAU - Fan, Yawei AU - Fan Y AD - Department of Oral and Maxillofacial Surgery, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi, China. FAU - Nan, Xinrong AU - Nan X AD - Department of Oral and Maxillofacial Surgery, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi, China. FAU - Fu, Rong AU - Fu R AD - School of Basic Medical Sciences, Shanxi Medical University Taiyuan 030001, Shanxi, China. LA - eng PT - Journal Article DEP - 20230515 PL - United States TA - Am J Cancer Res JT - American journal of cancer research JID - 101549944 PMC - PMC10244118 OTO - NOTNLM OT - Ly6D OT - chemoresistance OT - laryngeal squamous cell carcinoma OT - miR-509 OT - beta-catenin COIS- None. EDAT- 2023/06/09 06:41 MHDA- 2023/06/09 06:42 PMCR- 2023/05/15 CRDT- 2023/06/09 04:30 PHST- 2023/01/30 00:00 [received] PHST- 2023/04/25 00:00 [accepted] PHST- 2023/06/09 06:42 [medline] PHST- 2023/06/09 06:41 [pubmed] PHST- 2023/06/09 04:30 [entrez] PHST- 2023/05/15 00:00 [pmc-release] PST - epublish SO - Am J Cancer Res. 2023 May 15;13(5):2155-2171. eCollection 2023.