Department of Head and Neck Surgery, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, No.30 North Tongyang Road, Pingchao, 226361, Nantong, Jiangsu, China.
Department of Pathology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, No.30 North Tongyang Road, Pingchao, 226361, Nantong, Jiangsu, China.
Cell Death Dis. 2020 Sep 11;11(9):743. doi: 10.1038/s41419-020-02827-w.
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.
外泌体长非编码 RNA（lncRNA）是介导肿瘤微环境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中 PTC 差异表达 lncRNA 的结果，我们发现 DOCK9-AS2 在 PTC 中上调，并在 PTC 患者的血浆外泌体中升高。功能上，DOCK9-AS2 敲低可降低 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 以提高 PTC 细胞的干性。机制上，DOCK9-AS2 与 SP1 相互作用，诱导连环蛋白 beta 1（CTNNB1）转录，并吸附 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 激活了 Wnt/β-catenin 通路，加重了 PTC 的进展，表明 DOCK9-AS2 是 PTC 治疗的潜在靶点。
