Background: Long non-coding RNAs (lncRNAs) are regulatory molecules that have multifaceted impacts on the carcinogenic molecular landscape—with pathologic consequences when aberrantly expressed. Anaplastic thyroid cancer (ATC) is a rapidly progressing and highly lethal malignancy, with mortality rates approaching 100%. The molecular/transcriptomic signature of ATC has significant gaps in understanding; thus, a comprehensive study of ATC non-coding RNA transcript regulation is necessary.Results: The lncRNA Double Homeobox A Pseudogene 10 (DUXAP10) was identified in patient genomic datasets as a highly upregulated transcript in ATC vs. normal thyroid tissue. DUXAP10 expression was transcriptionally repressed with CRISPR-interference (CRISPRi), and data supports an extensive role of DUXAP10 in several cancer-promoting phenotypes in ATC, both in vitro and in vivo. Our two DUXAP10-CRISPRi cell lines significantly reduced the rapid growth and metastatic behaviors characteristic of ATC, affecting proliferation, viability, clonogenicity, apoptosis, invasion, migration, tumorigenesis, and metastasis.Conclusion: Thus, DUXAP10 is a proposed prognostic marker and therapeutic target for ATC disease propagation and progression.
背景：长链非编码RNA（lncRNA）作为调控分子，对致癌分子景观具有多层面影响，其异常表达会导致病理后果。间变性甲状腺癌（ATC）是一种进展迅速、致死率极高的恶性肿瘤，死亡率接近100%。目前对ATC的分子/转录组特征认知存在显著空白，因此有必要对ATC非编码RNA转录调控进行全面研究。 结果：通过患者基因组数据分析发现，与正常甲状腺组织相比，长链非编码RNA双同源盒A假基因10（DUXAP10）在ATC中呈现显著高表达。利用CRISPR干扰技术（CRISPRi）对DUXAP10表达进行转录抑制，数据显示DUXAP10在体外和体内实验中均对ATC的多种促癌表型具有广泛调控作用。我们构建的两个DUXAP10-CRISPRi细胞系显著降低了ATC特有的快速生长和转移行为，影响包括增殖、活力、克隆形成、凋亡、侵袭、迁移、肿瘤发生和转移等多个过程。 结论：因此，DUXAP10可作为预测ATC疾病扩散和进展的预后标志物及潜在治疗靶点。
Long Non-Coding RNA DUXAP10 Promotes Tumorigenesis and Metastasis in Anaplastic Thyroid Cancer
肿瘤(癌症)患者之家