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

作者：Li, Rui; Chen, Shuwei; Zhan, Jiandong; Li, Xinghua; Liu, Wenlin; Sheng, Xiaoli; Lu, Zhongming; Zhong, Rong; Chen, Liangsi; Luo, Xiaoning; Hu, Yameng; Ouyang, Ying; Liu, Tao^*; Zhang, Quan^*; Zhang, Siyi^*

来源：Cell Death & Disease, 2020, 11(1): 41.

DOI：10.1038/s41419-020-2232-7

• CANCER STEM-CELLS
• SIGNALING PATHWAY
• DISCOVERY
• PROMOTES

Laryngeal 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.

• 单位
  青岛大学; 中山大学; 广州医学院; 6; 广东省人民医院