Exosomal long non-coding RNAs (lncRNAs) are crucial factors that mediate the extracellular communication in tumor microenvironment. DOCK9 antisense RNA2 (DOCK9-AS2) is an exosomal lncRNA which has not been investigated in papillary thyroid carcinoma (PTC). Based on the result of differentially expressed lncRNAs in PTC via bioinformatics databases, we discovered that DOCK9-AS2 was upregulated in PTC, and presented elevation in plasma exosomes of PTC patients. Functionally, DOCK9-AS2 knockdown reduced proliferation, migration, invasion, epithelial-to-mesenchymal (EMT) and stemness in PTC cells. PTC-CSCs transmitted exosomal DOCK9-AS2 to improve stemness of PTC cells. Mechanistically, DOCK9-AS2 interacted with SP1 to induce catenin beta 1 (CTNNB1) transcription and sponged microRNA-1972 (miR-1972) to upregulate CTNNB1, thereby activating Wnt/β-catenin pathway in PTC cells. In conclusion, PTC-CSCs-derived exosomal lncRNA DOCK9-AS2 activated Wnt/β-catenin pathway to aggravate PTC progression, indicating that DOCK9-AS2 was a potential target for therapies in PTC.

外泌体长链非编码 RNA (lncRNA) 是介导肿瘤微环境中细胞外通讯的关键因素。DOCK9 反义 RNA2 (DOCK9-AS2) 是一种外泌体 lncRNA，尚未在甲状腺乳头状癌 (PTC) 中进行研究。基于生物信息学数据库对 PTC 中 lncRNA 差异表达的结果，我们发现 DOCK9-AS2 在 PTC 中上调，并且在 PTC 患者的血浆外泌体中呈现升高。在功能上，DOCK9-AS2 敲低减少了 PTC 细胞的增殖、迁移、侵袭、上皮间充质 (EMT) 和干性。PTC-CSCs 传递外泌体 DOCK9-AS2 以改善 PTC 细胞的干性。从机制上讲，DOCK9-AS2 与 SP1 相互作用以诱导连环蛋白 beta 1 (CTNNB1) 转录并海绵化 microRNA-1972 (miR-1972) 以上调 CTNNB1，从而激活 PTC 细胞中的 Wnt/β-catenin 通路。总之，PTC-CSCs 衍生的外泌体 lncRNA DOCK9-AS2 激活 Wnt/β-catenin 通路加速 PTC 进展，表明 DOCK9-AS2 是 PTC 治疗的潜在靶点。