Long noncoding RNA FOXD2-AS1 enhances chemotherapeutic resistance of laryngeal squamous cell carcinoma via STAT3 activation

Abstract

AbstractLaryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer. Despite recently improved management of LSCC, chemotherapy resistance of patients remains a challenge. In this study, we identified that long noncoding RNA FOXD2-AS1 regulates LSCC therapeutic resistance by augmenting LSCC stemness. LSCC chemotherapy-resistant patients showed increased FOXD2-AS1 expression compared with that in chemotherapy-sensitive patients, which predicted poor prognosis. Gain- or loss-of-function experiments showed that upregulated FOXD2-AS1 maintained cancer stemness, reducing the response to chemotherapy, while FOXD2-AS1 downregulation had the opposite effects. FOXD2-AS1 acted as a scaffold for STAT3 and PRMT5, promoting STAT3 transcriptional activity, which is essential to maintain cancer stemness and promote chemotherapeutic resistance. Interfering with FOXD2-AS1 using short hairpin RNA rescued LSCC’s chemotherapeutic sensitivity. Thus, FOXD2-AS1 promotes LSCC chemotherapeutic resistance and is an upstream activator of STAT3, making FOXD2-AS1 a potential therapeutic target to improve the chemotherapy effect in LSCC patients.